Environmental Enrichment Research Articles

Forensic Hypoglycaemia & Neuroglycopenia — A Clinical Legal Social Endocrinology Challenge for 2024, Forensic Law in Hypoglycaemia 4

The author, Derek Beatty, was diagnosed with T1D Diabetes 45 years ago when living in High Wycombe, Buckinghamshire, England. Symptoms of thirst, tiredness, difficulty in reading small print, led to GP doctor consultation with fasting blood glucose Biochemistry tests. Possible Genetic Inheritance may have contributed to reduced Immunogenic resistance to infection possibly triggered from business travel to several African Countries including Kenya, Zambia, Nigeria, Sudan, Egypt, South Africa. Add the trauma as witness to a fatal car crash in Bricket Wood, St Albans, when a driver of a Rolls Royce crashed into the rear of a lorry in the dark on an October afternoon. With a natural Adrenalin trigger to help in an emergency and First Aid training when in a Scout Group in Edinburgh, to stop and assist, comfort the car driver, shout for an ambulance when others appeared. An ambulance arrived promptly (before the era of Mobile Phones), Paramedics took over with hospital transfer. This frightening event has left a vivid memory flashback scar along with near fatal Hypoglycaemia with Neuroglycopenia scars. The Police called 3 days later and requested a witness statement. There was no hesitation to be able to help. When asked about the car driver welfare the answer was that he had suffered severe neurological injury and sadly died. What followed was a correct Fatal Accident Inquiry before a Coroner identifying Accidental Death. With courage the wife and family spoke after to thank me for doing my best to help save the driver, but sadly he had passed. We hope and pray he rests in peace. This tragic experience has left a strong sense of courage and determination in the belief that prevention is better than cure. When, and if tragedy occurs, what might have been the cause always helps in learning and education and often offers future opportunity to enable prevention. We can learn from tragedy and take steps to forensically identify cause and seek to prevent recurrence. The experience of near fatal Diabetes Hypoglycaemia and Neuroglycopenia caused by ignorance and failure to educate a family what to do in a diabetes hypoglycaemia emergency involving the Hormone Insulin with NHS GP mismanagement and Gross Negligence in Public Office cover up, when combined with an Addisonian Adrenalin Crisis, both with Neuroglycopenia and Simultaneous, has led to 30 years forensic research of the event cause with identified errors in Law justifying disclosure and loss recovery from those responsible for legal errors. Today with global interest and helpful personal clinical support from an excellent Diabetes Endocrinology Team of Clinicians and Nurses in Edinburgh and recognition with interest from many clinicians and nurses worldwide of the importance of this work has enhanced personal positivity to succeed and Win in Insulin Chicanes when at the same time treating an incurable long term health condition requiring daily injections of the hormone Insulin platformed with dose adjustment to target normoglycaemia and accommodate lifestyle while addressing insulin dose and type; exercise; diet; differences in carbohydrate and fat content in foods; interest in Keto style diet; fruit; vegetables; food sugar content; adverse stress: happiness; family and friendship encouragement and support; education of damage of excess alcohol; smoking; recreational drugs; and the link to the medical mystery. Summary review of Virological attack associated with Obesity, Overeating, Alcohol, risk of Foetal Alcohol Spectrum Disorder, Smoking, triggers for Parkinson’s Disease, Dyslexia, certain Ophthalmic conditions with possible links e.g., Nystagmus linked to Dyslexic, Genetically Inherited Addison’s Disease possibly from India after discovery by Thomas Addison in 1860 and add the Insulin Journey from discovery Banting, Best, Macleod, Collip, 1922, and the World’s First Hypoglycaemia Event with Neuroglycopenia experienced as a Clinical Event by Dr Jim Gilchrist and in L:aw recognised as Such by Banting, Best, Macleod, Collip, and Toronto Police, Canada at the time. Yes, Insulin can be used as a Poison, but it is a lifesaving Hormone for which today in 2024 all T1D Diabetes patients are exceedingly grateful for the research of over 100 years ago. One must never describe in Law Insulin as a Poison without good cause and reason. Insulin is a Hormone. This is important especially in tragic cases in pregnancy when Gestational Diabetes can occur leading to neonate and young baby infection and on occasion fatality. In 2023 I have experienced Blue Toe Syndrome associated with negative test Long COVID caused by vascular disturbance at toe extremity and Quinsi, very rare in long term Diabetes, sometimes in Tonsilitis during teenage and early adult life, but likely identified as Virological infection caused by Long COVID. Was prevention of Hypoglycaemia Unawareness in 1987–1994 possible? How do we discover? We need to research. We need social recognition and understanding in 2024 as we use this experience to better understand Clinical Hypoglycaemia and Neuroglycopenia in Law. 2023 published awareness of Hypoglycaemia, IDF INTERNATIONAL DIABETES FEDERATION with Immunogenic Issues in Diabetes and Addison’s Disease, has identified implications for COVID-19 Public Health Inquiry Investigation in Scotland. Forensic Aspects of Hypoglycaemia 4, now explores CPS Crown Prosecution Service and Court Reference Redacted in St Albans, Hertfordshire, England, to Correct Errors in Law identified from 1989 when a Law Society registered solicitor in Knutsford, Cheshire, who on the balance of probability, was aware that the Law Society in England at the time had allocated £500,000 in Public Funds to assess whether a case existed to identify Marketing and Safety adverse experience of Hypoglycaemia Unawareness? Investigation led to instances of personal injury and cases of unexplained death in bed syndrome to address a claim for damage experience against the Pharmaceutical Industry. A licence to market BHI Insulin on 26 August 1982 was given after close forensic safety consideration by application to the MHRA at the Department of Health, London. The Licence was granted with provisions that prescribing GP General Practitioner doctors reduced the Insulin dose by up to 20% when prescribed to T1D diabetes patients treated with Porcine or Beef Insulin, prescribed BG Blood Glucose monitoring medical devices to the patient, and provide clear education to the Patient and family members living with the Diabetes Patient, providing care for the patient, and knowing exactly what to do in a Diabetes Hypoglycaemia Emergency, and by default an Endocrine Red Alert Adrenalin Addisonian Crisis. On all counts the GP Practice in St Albans and Bricket Wood, Hertfordshire, failed miserably. When consulted in 1989 by the patient’s wife and sister-in-law the Knutsford solicitor firm failed to disclose known Law Society Investigation update involving Hypoglycaemia and education to the solicitor clients, the patient’s Wife and Sister-in-Law, and instead sent a libelous letter to the patient in 1989 with redisclosure in 1994. Character defamation of the patient in 1989 and 1994 is forensically identified in 2024 as clinical behavioural temporary mental health when in a state of hypoglycaemia unawareness and can be demonstrated in the animal rat model showing inferior quality Purkinje Cell Environmental Enrichment with insulin overdose or underdose leading to hyperglycaemia which when under corrected can lead to diagnose of T2D Type 2 Diabetes often associated with diet, lack of exercise, poor keto diet experience, alcohol abuse leading to obesity. In 2000, a request to the Court for medical notes disclosure was described as a ‘Fishing Trip’. Again in 2005 an Insurance Broker completely ignorant of Diabetes and Hypoglycaemia misled the court. Disclosure December 2020 by a Transaction Director, London, of the Firm EY, is identified as failure to identify and seek NHS help to address likely Genetically Inherited Addison’s Disease in an NHS patient, first suspected in 1994 when the GP Practice failed to act, then in March 1996 when the Official Solicitor was invited to investigate with referral failure. 2024 Forensic Analysis has identified opportunities to act and correct errors in law, nothing was done, why? In 2024 we investigate the cause of Suicide on 11 October 2020 in Alban Manor Nursing Home, St Albans, during COVID-19 Pandemic of Addison’s Disease Patient. Despite aged 79 her life could have been saved but alleged negligence in breach of the Mental Health Act 1983 caused the death with failure to take into account warnings from the Banting Lecture 1994 Hypoglycaemia, Real or Unreal, Lawful or Unlawful with Addison’s Disease Suicide. Under European Human Rights Law, The Human Rights Act 1998, and European Convention on Human Rights, a Public Immunity Argument exists to publish to learn from experience to prevent reoccurrence with implications to assist COVID-19 Public Health Inquiry Investigation.

Targeting epigenetic mechanisms in amyloid-β–mediated Alzheimer’s pathophysiology: unveiling therapeutic potential

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer’s disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease. We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

Preening cups in duck housing are associated with an increase in central dopamine activity that suggests a negative affective state

Preening cups are a form of environmental enrichment that provides Pekin ducks a semi-open water source to express their natural behaviors. We recently observed that preening cups may increase feather pecking behaviors in ducks. Thus, we set out to determine if this form of enrichment can impact the affective state of Pekin ducks. To accomplish this goal, we evaluated the effect of preening cups on serotonin (5-HT) and dopamine (DA) turnover via mass spectrometry and their respective synthetic enzyme gene expression via qRT-PCR. Our study investigated the link between aggressive pecking with levels and activity of brain 5-HT and DA. Brain 5-HT and DA levels and activity have been established for decades to be associated with affective states. Grow-out Pekin ducks (n = 260) were housed at Purdue and raised per industry standards. On day 18, brains were collected from ducks in pens before preening cups were placed (PRE, n = 6) and, again on day 43, in pens with (PC, n = 6) and without (CON, n = 6) preening cups. Brains were dissected into right and left halves, then further microdissected into 4 brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), diencephalon (DI), and forebrain (FB). The right hemisphere was used for mass spectrometry to determine the neurotransmitter concentration (ng/mg of tissue) and those concentrations were applied to neurotransmitter turnover equations. There were no differences across treatments for 5-HT turnover in any brain area. There were differences in DA turnover across age (P = 0.0067) in the CM and across treatments (P = 0.003) in the RM. The left hemisphere of the brain was used to perform qRT-PCR on the genes of 5-HT and DA production enzymes. Within the CM, day 43 duck brains had increased (P = 0.022) tryptophan hydroxylase and tyrosine hydroxylase relative mRNA levels. All other brain areas showed no differences. Our data suggest that ducks housed with preening cups and that showed increased feather pecking are associated with increased brain DA activity. The increased DA in the brain may lead to a predisposition for increased aggression in the form of feather pecking.

Enriched environment treatment promotes neural functional recovery together with microglia polarization and remyelination after cerebral ischemia in rats

BackgroundMicroglia activation and oligodendrocyte maturation are critical for remyelination after cerebral ischemia. Studies have shown that enriched environment (EE) can effectively alleviate stroke-induced neurological deficits. However, little is known about the mechanism associated with glial cells underlying the neuroprotection of EE. Therefore, this study focuses on investigating the effect of EE on activated microglia polarization as well as oligodendrogenesis in the progress of remyelination following cerebral ischemia. MethodsThe ischemia/reperfusion (I/R) injury model was established by middle cerebral artery occlusion (MCAO) in rats. Animals executed 4 weeks of environmental intervention after performing MCAO or sham surgery and were divided into sham, MCAO, and MCAO+EE groups. Cognitive function, myelin damage, microglia activation and polarization, inflammation, oligodendrogenesis, remyelination, and protein expression of the PI3K/AKT/GSK3β signaling pathway were determined. ResultsThe staining of NeuN indicated that the infarct size of MCAO rats was decreased under EE. EE intervention improved animal performance in the Morris water maze test and novel object recognition test, promoting the recovery of cognitive function after I/R injury. EE treatment alleviated myelin damage in MCAO rats, as evidenced by the lower fluorescence intensity ratio of SMI-32/MBP in MCAO+EE group. EE increased the fluorescence intensity ratio of NG2+/Ki67+/Olig2+, MBP, and MOG, enhancing the proliferation and differentiation of OPCs and oligodendrogenesis after MCAO. In terms of remyelination, more myelinated axons and lower G/ratio were detected in MCAO+EE rats compared with MCAO group. Moreover, EE treatment decreased the number of Iba1+/CD86+ M1 microglia, increased the number of Iba1+/CD206+ M2 microglia, and suppressed the inflammation response after I/R injury, which could be attributed to the augmented expression of PI3K/AKT/GSK3β axis. ConclusionEE improved long‑term recovery of cognitive function after cerebral I/R injury, at least in part by promoting M2 microglia transformation through activation of the PI3K/AKT/GSK3β signaling pathway, inhibiting inflammation to provide a favorable microenvironment for oligodendrocyte maturation and remyelination. The effect of the EE on myelin and inflammation could account for the neuroprotection provided by EE.

Is Early-Life Enrichment Associated With Better Cognitive Function Among Older Adults? Examining Home and School Environments.

Objectives: We examine whether early-life enrichment, involving varied and stimulating activities to enhance cognitive function during childhood and adolescence, is associated with cognitive function in later life and whether the benefits persist over time. Methods: Growth curve models were used to examine up to five waves of data from the Health and Retirement Study-a nationally representative survey of adults 50years and older (N = 10,070). We constructed separate measures of early-life enrichment to distinguish sources of influence (i.e., enriched home environment and enriched school environment). Global cognitive function was assessed with a modified version of the Telephone Interview for Cognitive Status. Results: Greater enrichment in each environment was incrementally associated with better cognitive function at baseline, but enrichment was not associated with change in cognitive function over time. Discussion: Receiving enrichment from multiple environments during sensitive periods of cognitive development may be advantageous for cognitive functioning in later life.

Partially divided caging reduces overall aggression and anxiety which may indicate improved welfare in group housed male C57BL/6J mice

Deciding which environmental enrichment is used in mouse caging is often subjective, with cost frequently prevailing over welfare benefits, including aggression and anxiety. While many devices introduced to encourage natural behaviors and reduce aggression show mixed results, we have previously demonstrated significant reductions in aggressive behavior between group-housed male mice housed in partially divided caging. To further assess behavior, we have raised male C57BL/6J mice in either partially divided caging or in standard caging with no divider. Animal behavior was tested on rotarod, open field, novel object recognition, elevated plus maze, and Y maze. Body weights were taken weekly beginning at weaning and bite wounds were counted weekly beginning at 133 days old. Aggressive behavior was recorded weekly beginning at 133 days old. Results indicated significantly less anxiety in the elevated-plus maze, statistically fewer bite wounds, and a statistically significant decrease in aggressive behaviors of mice in partially divided caging compared to mice in standard cages. We conclude that reductions in anxiety, aggressive behavior, and bite wounds may indicate improved overall welfare for non-sibling, group housed male mice.

Greater Expectations: An Appreciative Inquiry into How UK Home-Educating Families Support Their Children’s Learning

Elective home education is a significant aspect of the UK educational system, yet dedicated research on this topic is limited. This study, employing Appreciative Inquiry, explored the best practices perceived by 90 UK home-educating parents. It uncovered diverse strategies, emphasising the importance of resources such as technology, curricula, and collaborative efforts within home education co-operatives. Parents stressed the value of flexible learning environments and strong family commitment, envisioning a future with an enhanced home learning atmosphere and government and school support. They recommended concrete guidance for prospective home-educating parents, focusing on comprehensive child development. Ultimately, families aspired to shape a future for home education that prioritises enriched learning environments, broader societal recognition, and practical support for those embarking on the home education journey. The study’s findings have implications for children’s development, facilitating collaboration between homes and schools, as well as partnerships between families and educators.

Management of Donkeys in Assisted Interventions: A Snapshot.

People working in the field of Animal-Assisted Interventions (AAIs) often state that they perceive animal welfare as a matter of paramount importance; nevertheless, most scientific literature focuses on the effectiveness of interventions from the user's perspective. Before focusing on the animals' management and welfare during their interactions with users, it is important to ensure animal welfare during their "ordinary lives". This article reports information and considerations about the management of donkeys involved in AAIs in Northern Italy. Six facilities with several years of experience in Donkey-Assisted Interventions were visited for the purpose of an initial data collection regarding the management of donkeys involved in AAIs. Some knowledge gaps regarding the nutritional needs of the donkey and its preventive medicine have been identified; this study also highlighted a need for efforts to create a more stimulating and enriched environment for animals involved in AAIs. Some possible areas for improvement in the management of donkeys involved in AAIs have been highlighted. Further studies are necessary to provide a more comprehensive picture of the welfare of donkeys involved in this context.

Brief exposure to enriched environment rapidly shapes the glutamate synapses in the rat brain: A metaplastic fingerprint.

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and, in turn, modulate reward-seeking behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes in glutamatergic mPFC, NAc and Hipp. Such changes are area-specific and involve postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins, thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to dynamically modulate the glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate rewarding and memory processes.

Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.

Magnetite modified zeolite as an alternative additive to promote methane production from anaerobic digestion of waste activated sludge

Methane recovery from bio-wastes is one promising renewable energy to relieve the energy crisis faced around the world. Zeolite is one of attractive exogenous additives for promoting methane production from anaerobic digestion due to its potentials in regulating microorganism enrichment and anaerobic environment. However, the poor electron mediated ability limited its positive effects. Hence, this study hypothesized that the electron mediated ability of zeolite would be improved by loading magnetite, thereby generating more positive impacts on the performance of sludge anaerobic digestion. Compared to control group, magnetite modified zeolite (MZ) effectively improved methane yield by 37.4%. The reason was that the electron mediated ability and adsorption capacity of zeolite were improved by loading magnetite, facilitating the degradation of refractory organics and the conversion of volatile fatty acids. Moreover, the activities of cytochrome c and F420 increased by 33.3% and 29.8% with MZ additive, contributing to stimulating efficient electron transfer process. In addition, the electro-active genera were enriched, such as Bacteroidetes_vadinHA17, Methanobacterium, and Methanosaeta, and the direct interspecies electron transfer was possibly established for methanogenesis with the help of MZ. This study will provide valuable references for the application of zeolite in anaerobic digestion.

Research Proposed: Further study into the Pathway Downstream Sperm miR212/132 in EE-induced Phenotype Inheritance

It has been shown that some environmental factors can lead to changes in an organism’s genetic materials and, therefore, be inherited by the following generations. This inheritance form shows evolutionary and clinical implications, suggesting value for research. In a previous study (Benito, 2018), it has been proved that miR212/132 plays an important role in mediating Environmental Enrichment (EE)-induced phenotype inheritance. Proposing for further research, this article aims at studying the pathway downstream of miR212/132. Two targets of miR212/132, Dnmt3a and Rsf1, are considered possible downstream factors, and some changes in DNA methylation or histone modification are regarded as possible downstream effects that lead to EE phenotype in offspring. Experiments are designed accordingly.

The Comparative Effect of Occupational and Musical Enrichment on Fecal Glucocorticoid Metabolite Levels in a Captive Colony of Stumptail Macaques (Macaca arctoides).

Environmental enrichment improves captive animal welfare by reducing stress-related behaviors. Previous studies in a captive colony of stumptail macaques (Macaca arctoides) reported a reduction of aggression, coprophilia, and stereotypic behaviors after an occupational enrichment program; however, the effect on stress hormones such as glucocorticoids has not been investigated yet. The goal of this study was to compare the effect of sex, age, and social rank on changes in fecal glucocorticoid metabolites (fGCM) after applying two kinds of enrichments (occupational vs. musical) in a captive colony of stumptail macaques. We collected 234 fecal samples from 25 stumptail macaques under the following conditions: (1) basal (no enrichment), (2) three weeks of occupational enrichment, and (3) three weeks of relaxing/classical music. The Generalized Estimated Equation Model showed an increase in fGCM levels after the occupational enrichment only in adult subjects (p = 0.003 compared to basal). The fGCM levels reached by the adults after the occupational enrichment was higher than that of juveniles (p = 0.002) and subadults (p = 0.02). Occupational and musical enrichment decreased fGCM levels only in middle-ranking individuals (p < 0.001 and p = 0.013, respectively). No sex differences were found. In conclusion, there were age and rank differences in individuals' physiological reactivity to the effects of environmental enrichment which need to be considered when planning enrichment programs.

Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion

Neurovascular unit mural cells called ‘pericytes’ maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25–40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 ± 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection.

Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

Rearticulating theory and methodology for perezhivanie and becoming

Taking up Lemke’s (2000) critical questions of how moments add up to lives and social life, we articulate theoretical and methodological frameworks for perezhivanie and becoming, challenging binaries that splinter entangled flows of perezhivanie into frozen categories. Working from a flat CHAT notion of assemblage to develop an ontology of moments, we stress consequentiality, arguing it emerges in intersections of embodied intensities (not only affective, but also indexical, intra-actional, and historic), the dispersed bio-cultural-historical weight of artifacts and practices, and dialogic resonances across moments. Methodologically, we take an ethico-onto-epistemological perspective to systematically study perezhivanie. The bio-ecological model of rich environments (centered around meaningful complexity, agency, and individual optimization) offers both a key framework for understanding becoming and a design framework for transdisciplinary realizations of ethico-onto-epistemological practice. We illustrate these frameworks with examples from four research projects: a university physics lab group doing and writing an experiment, a former pastor managing bipolar disorder and rejecting faith, a sustained social justice education program at a university, and intersections of aging policies, media representations, and stroke survival in Brazil. Finally, we argue that an ontology of moments centered on consequentiality can illuminate perezhivanie's relationship to becoming and that the model of enriched environments offers metrics to assess and design environments.

Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats

A typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This study stripped out the different components of EE into physical environmental enrichment (PE) and social environmental enrichment (SE), and compared the neuroprotective effects of PE, SE and typical EE (PSE) in CCH. The results of novel object recognition and Morris water maze tests showed that PE, SE, and PSE improved cognitive function in CCH rats. Additionally, Nissl and TUNEL staining revealed that three EEs reduced neuronal loss in the hippocampus. PSE exhibited superior neuroprotective and functional improvement effects compared to PE and SE, while there was no significant difference between PE and SE. Furthermore, three EEs reduced lipid peroxidation in the hippocampus with decreasing the levels of MDA and increasing the activities of SOD and GSH. The expression of SLC7A11 and GPX4 was increased, while the level of p53 was reduced in three EEs. This suggested that three EEs inhibited ferroptosis by maintaining the redox homeostasis in the hippocampus. Three EEs reduced the levels of IL-β, TNF-α, and IL-6, thereby inhibiting neuroinflammation. Additionally, Western blotting and immunofluorescence results indicated that three EEs also inhibited the TLR4/MyD88/p38MAPK signaling pathway. These findings collectively demonstrated that the three EEs alleviated hippocampal ferroptosis and neuroinflammation in CCH rats, thereby reducing neuronal loss, which might be associated with the inhibition of the TLR4/MyD88/p38MAPK signaling pathway. Moreover, the study results supported that it is only through the combination of physical exercise and social interaction that the optimal neuroprotective effects can be achieved. These findings provided valuable insights for the prevention and treatment of vascular cognitive impairment.

Effects of Environmental Enrichments on Welfare and Hepatic Metabolic Regulation of Broiler Chickens.

The aims of this study were to find suitable environmental enrichment (EE) and evaluate the combined effect of two EEs, variable light intensity (VL) lighting program and EH, on mental health and hepatic metabolic regulation in commercial broilers. To find the advantageous EEs for broilers, three different EEs (board, hut, and ramp) were tested in trial 1. EEs were placed and the engagement of birds to EEs, dustbathing behavior, and daily physical activity were observed. Birds treated with huts showed higher engagement than the board- or ramp-treated birds (p < 0.05). The results of dustbathing behavior and daily physical activity indicated that the environmental hut (EH) is the most favorable enrichment for broilers. In the second trial, to test the effect of EHs on mental health and hepatic metabolic conditions, the brain and liver were sampled from the four treatment birds (20 lx_Con, 20 lx_Hut, VL_Con and VL_Hut) on day 42. The lower expression of TPH2 (tryptophan hydroxylase 2) of VL_Hut birds than those of VL_Con and 20 lx_Hut treated birds suggests the combining effect of EHs with the VL lighting program on the central serotonergic homeostasis of broilers. Reduced expressions of TH (tyrosine hydroxylase), GR (glucocorticoid receptor), BDNF (brain-derived neurotrophic factor) of VL_Hut treated birds compared to those of VL_Con and 20 lx_Hut birds suggest lower stress, stress susceptibility, and chronic social stress in VL_Hut treated birds. The expression of CPT1A (carnitine palmitoyl transferase 1) increased over three-fold in the liver of VL_Con birds compared to 20 lx_Con birds (p < 0.05). EHs treatment in VL birds (VL_Hut) significantly decreased CPT1A but not in 20 lx birds (20 lx_Hut). The expression of ACCα (acetyl-CoA carboxylase alpha) was significantly decreased in VL_Con birds compared to 20 lx_Con birds. There was no significant difference in the hepatic FBPase (fructose-1,6-bisphosphatase), GR, and 11β-HSD1 (11 β-hydroxysteroid dehydrogenease-1) expression between 20 lx_Con and VL_Con birds, but EHs significantly stimulated GR in 20 lx_Hut birds, and stimulated FBPase and 11β-HSD1 expression in the VL_Hut birds compared to 20 lx_Con birds, suggesting that the VL lighting program reduced fatty acid synthesis and increased fatty acid β-oxidation in the broilers' liver and VL_Hut improved the hepatic de novo glucose production. Taken together, the results suggest that the stimulated voluntary activity by EHs in the light-enriched broiler house improved mental health and hepatic metabolic function of broilers and may indicate that the improved hepatic metabolic function contributes to efficient nutritional support for broilers.

Maternal environmental enrichment protects neonatal brains from hypoxic-ischemic challenge by mitigating brain energetic dysfunction and modulating glial cell responses

There is evidence that maternal milieu and changes in environmental factors during the prenatal period may exert a lasting impact on the brain health of the newborn, even in case of neonatal brain hypoxia-ischemia (HI). The present study aimed to investigate the effects of maternal environmental enrichment (EE) on HI-induced energetic and metabolic failure, along with subsequent neural cell responses in the early postnatal period. Male Wistar pups born to dams exposed to maternal EE or standard conditions (SC) were randomly divided into Sham-SC, HI-SC, Sham-EE, and HI-EE groups. Neonatal HI was induced on postnatal day (PND) 3. The Na+,K+-ATPase activity, mitochondrial function and neuroinflammatory related-proteins were assessed at 24 h and 48 h after HI. MicroPET-FDG scans were used to measure glucose uptake at three time points: 24 h post-HI, PND18, and PND24. Moreover, neuronal preservation and glial cell responses were evaluated at PND18. After HI, animals exposed to maternal EE showed an increase in Na+,K+-ATPase activity, preservation of mitochondrial potential/mass ratio, and a reduction in mitochondrial swelling. Glucose uptake was preserved in HI-EE animals from PND18 onwards. Maternal EE attenuated HI-induced cell degeneration, white matter injury, and reduced astrocyte immunofluorescence. Moreover, the HI-EE group exhibited elevated levels of IL-10 and a reduction in Iba-1 positive cells. Data suggested that the regulation of AKT/ERK1/2 signaling pathways could be involved in the effects of maternal EE. This study evidenced that antenatal environmental stimuli could promote bioenergetic and neural resilience in the offspring against early HI damage, supporting the translational value of pregnancy-focused environmental treatments.

Impact of altered environment and early postnatal methamphetamine exposure on serotonin levels in the rat hippocampus during adolescence

BackgroundMethamphetamine (MA) is a highly abused psychostimulant across all age groups including pregnant women. Because developing brain is vulnerable by the action of drugs, or other noxious stimuli, the aim of our study was to examine the effect of early postnatal administration of MA alone or in combination with enriched environment (EE) and/or stress of separate housing, on the levels of serotonin (5HT) in the hippocampus of male rat pups at three stages of adolescence (postnatal day (PND) 28, 35 and 45). MA (5 mg/kg/ml) was administered subcutaneously (sc) to pups (direct administration), or via mothers' milk between PND1 and PND12 (indirect administration). Controls were exposed saline (SA). Pups were exposed to EE and/or to separation from the weaning till the end of the experiment.ResultsOn PND 28, in sc-treated series, EE significantly increased the muted 5HT in SA pups after separation and restored the pronounced inhibition of 5HT by MA. No beneficial effect of EE was present in pups exposed to combination of MA and separation. 5HT development declined over time; EE, MA and separation had different effects on 5HT relative to adolescence stage.ConclusionsPresent study shows that MA along with environment or housing affect 5HT levels, depending on both the age and the method of application (direct or indirect). These findings extend the knowledge on the effects of MA alone and in combination with different housing conditions on the developing brain and highlight the increased sensitivity to MA during the first few months after birth.