Brain Neurotransmitter Levels Research Articles

Therapeutic efficacy of amygdaline and amygdaline-loaded niosomes in a rat model of Alzheimer’s disease via oxidative stress, brain neurotransmitters, and apoptotic pathway

Abstract Background Alzheimer’s disease (AD) is a specific form of neurodegeneration that is marked by impairments in memory and cognition. Exposure to some metal toxins, such as aluminum (AL), was directly linked to the onset of AD as it was hosted in the body via several exposure routes and can change the permeability and cross the blood–brain barrier. Due to amygdaline’s existence, apricot kernel therapy for AD is believed to have been established to be successful in numerous investigations. Amygdaline has been shown to have antioxidant effects that mitigate oxidative damage, and free radicals scavenger activity, as well as amygdaline niosomes as a nanoparticle has been found to improve the drug’s efficiency and selectivity. The objectives of this investigation are to study the neuroprotective role of amygdaline, and amygdaline-loaded niosomes formulation in the diminishment of the incidence of AD in neurotoxin (aluminum chloride; AlCl3) AD animal model. Results Data revealed that AlCl3 caused cognitive decline that was confirmed by cognitive behavioral tests (novel object and Y-maze); biochemical disturbances that include marked oxidative stress (elevated malondialdehyde and reduced total antioxidant capacity), reduced acetylcholinesterase, and brain monoamines levels (nor adrenalin; 4-dihydroxyphenylacetic acid; 5-hydroxytryptamine /serotonin; dopamine), and gene regulation upset (down-regulated transcript levels of acetylcholinesterase; monoamine oxidase; BCL-2 and up-regulated transcript levels of BAX), as well as neurodegenerative changes were observed in the hippocampus of AlCl3-treated rats. Treatment with amygdaline and amygdaline-loaded niosomes formulation improved working memory and recognition, alleviated oxidative stress, and restored the levels of brain monoamines and neurotransmitters. Moreover, gene expression data showed a significant down-regulation of BAX, while BCL-2, acetylcholinesterase, and monoamine oxidase were significantly up-regulated. Additionally, the histopathological examination showed reduced neurodegeneration. Conclusion Conclusively, it was evident that amygdaline and amygdaline-loaded niosomes formulation possess a neuroprotective and cognitive enhancement role in AD via their potent antioxidant potential, neurotransmitters, and gene expression regulations, as well as neural damage reduction capability. Graphical abstract

Neurobiological Changes Induced by Mindfulness and Meditation: A Systematic Review.

Background and Objectives: Meditation and mindfulness, rooted in ancient traditions, enhance mental well-being by cultivating awareness and emotional control. It has been shown to induce neuroplasticity, increase cortical thickness, reduce amygdala reactivity, and improve brain connectivity and neurotransmitter levels, leading to improved emotional regulation, cognitive function, and stress resilience. This systematic review will synthesize research on neurobiological changes associated with mindfulness and meditation practices. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases without any search time range. This review has been registered on Open OSF (n) GV2JY. Results: Mindfulness-Based Stress Reduction (MBSR) enhances brain regions related to emotional processing and sensory perception, improves psychological outcomes like anxiety and depression, and exhibits unique mechanisms of pain reduction compared to placebo. Conclusions: This review highlights that mindfulness, particularly through MBSR, improves emotional regulation and brain structure, reduces anxiety, and enhances stress resilience. Future research should focus on diverse populations and naturalistic settings to better understand and optimize these benefits.

L-theanine, the unique constituent of tea, improves neuronal survivability by curtailing inflammatory responses in MPTP model of Parkinson's disease

Discrete components of tea possess multitude of health advantages. Escalating evidence advocate a consequential association between habitual tea consumption and a subsided risk of Parkinson's disease (PD). l-theanine is a non-protein amino acid inherent in tea plants, which exhibits structural resemblance with glutamate, the copious excitatory neurotransmitter in brain. Neuromodulatory effects of l-theanine are evident from its competency in traversing the blood brain barrier, promoting a sense of calmness beyond enervation, and enhancing cognition and attention. Despite the multifarious reports on antioxidant properties of l-theanine and its potential to regulate brain neurotransmitter levels, it is obligatory to understand its exact contribution in ameliorating the pathophysiology of PD. In this study, MPTP-induced mouse model was established and PD-like symptoms were developed in test animals where an increasing dosage of l-theanine (5, 25, 50, 100 and 250 mg/kg) was intraperitoneally administered for 23 days. 50 and 100 mg/kg dosage of l-theanine alleviated motor impairment and specific non-motor symptoms in Parkinsonian mice. The dosage of 100 mg/kg of l-theanine also improved striatal dopamine and serotonin level and tyrosine-hydroxylase positive cell count in the substantia nigra. Most crucial finding of the study is the proficiency of l-theanine to diminish astroglial injury as well as nitric oxide synthesis, which suggests its possible credential to prevent neurodegeneration by virtue of its anti-inflammatory attribute.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors – including care, pup retrieval, and preference – as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa (Schenk) Wight

ObjectiveTo evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. MethodsModels of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. ResultsThis study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. ConclusionThe anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Robust congregation influences of AB-PINACA and MDMB-4en-PINACA inhalation on neurobehavioral and cardiac disorders in mice

BackgroundA novel category of unusual cannabinoid substances was created to serve as marijuana alternatives due to its widespread availability, low price, pleasurable effects, and difficulty to be detected in regular urine testing for drugs, although more potential for abuse, toxicity, and behavioral alterations can result. It is more hazardous to multiple organ systems and has higher CB1 and CB2 receptor affinities than natural cannabinoids. So, the abuse potential, toxicity, and cardiac and nervous systems health hazards of two popular street herbs (AB-PINACA and MDMB-4en-PINACA) have been evaluated in mice.MethodsThirty male mice were separated into three equally sized groups indiscriminately: the control group: received no treatments, the AB-PINACA-treated group, and the MDMB-4en-PINACA-treated group. Treated groups were exposed to the two herbs for two consecutive days via inhalation to simulate natural human exposure. Cannabinoid tetrad tests and anxiety-like behavior were performed. Serum samples were obtained for cardiac enzymes measurement. Heart and brain tissue samples were harvested for the determination of oxidative stress markers, brain neurotransmitters, and histopathological findings.ResultsNociception and hypothermia were significantly influenced by both treatments. The locomotor activity decreased significantly with AB-PINACA inhalation, while the cataleptic effect increased significantly with MDMB-4en-PINACA inhalation. In addition, both treatments induced anxiety-like behavior. Both treatments induced alterations in brain neurotransmitter levels (glutamate, dopamine, and serotonin) and cardiac enzyme levels (CK-MB, troponin I). Histological changes showed neurodegenerative, necrotic, and infracted heart myocytes and degenerated muscle fibers, particularly with MDMB-4en-PINACA inhalation.ConclusionsAcute inhalation of street herbs containing AB-PINACA and MDMB-4en-PINACA induced neurobehavioral and cardiac disturbances, which were evident by changes in behavior, brain neurotransmitters, and heart enzymes, in addition to the degenerative histopathological changes in the brain and heart.

Effect of butylphthalide on prevention and treatment of high altitude cerebral edema in rats

3-n-butylphthalide (NBP) contains one of the main active ingredients of celery seed. It has a series of pharmacological mechanisms, including reconstitution of microcirculation, protection of mitochondrial function, inhibition of oxidative stress, and inhibition of neuronal apoptosis. Based on the complex multi-targeting of NBP pharmacological mechanisms, the clinical applications of NBP are increasing, and more and more clinical studies and animal experiments have focused on NBP. In this study, we used male Sprague Dawley rats as an animal model to elucidate the intervention effect of butylphthalide on high altitude cerebral edema (HACE), and also compared the effect of butylphthalide and rhodiola rosea on HACE. Firstly, we measured the changes of body weight and brain water content and observed the pathological changes of brain tissues. In addition, the contents of inflammatory factors, oxidative stress and brain neurotransmitters were assessed by enzyme-linked immunoassay kits, and finally, the expression of apoptotic proteins in brain tissues was determined by western blotting. The results showed that NBP reduced brain water content, attenuated brain tissue damage, altered inflammatory factors, oxidative stress indicators, and brain neurotransmitter levels, and in addition NBP inhibited the expression of Caspase-related apoptotic proteins. Therefore, NBP has the potential to treat and prevent HACE.

Examining the Influence of Zinc Oxide Nanoparticles and Bulk Zinc Oxide on Rat Brain Functions: a Comprehensive Neurobehavioral, Antioxidant, Gene Expression, and Histopathological Investigation

The study aimed to assess the impact of zinc oxide nanoparticles (ZnONPs) on rats’ neurobehavior compared to bulk zinc oxide (BZnO). Thirty male Sprague-Dawley rats were randomly assigned to five groups. The control group received Tween 80 (10%), while the ZnONP groups were given ZnONPs at 5 and 10 mg/kg body weight dosages, and the bulk zinc oxide (BZnO) groups received BZnO at the same dosages. Behavioral observations, neurobehavioral examinations, and assessments of brain tissue oxidative markers, neurotransmitter levels, and histopathological changes were performed. The results indicated that ZnONP at a dosage of 5 mg/kg improved general behavior, locomotor activity, memory, and recognition and reduced fearfulness in rats. Conversely, the higher dosage of 10 mg/kg and the bulk form had adverse effects on general behavior, locomotor activity, and learning ability, with the bulk form demonstrating the most severe impact—znONP-5 treatment increased antioxidant enzyme levels and decreased inflammatory markers. BZnO-5 exhibited lower oxidative stress markers, although still higher than BZnO-10. Furthermore, ZnONP-5 and BZnO-5 increased neurotransmitter levels compared to higher dosages. ZnONP-5 upregulated the expression of brain-derived neurotrophic factor (BDNF) mRNA, while BZnO-5 showed increased BDNF mRNA expression and decreased expression of genes related to apoptosis and inflammation. In summary, ZnONPs at 5 mg/kg demonstrated positive effects on rat brain function and behavior, while higher dosages and the bulk form had detrimental effects. In conclusion, the studies emphasized the importance of further assessing various doses and forms of zinc oxide on brain health, highlighting the significance of dosage considerations when using nanomaterials.

Neurochemical Effects of the Adipokinetic Hormone/Red Pigment Concentrating Hormone Family of Peptides in MK-801-Induced Schizophrenia Rat Model

Objective: Adipokinetic hormone (AKH) plays a role in sugar and lipid metabolism in insects. Previous studies of AKH showed memory improvements in a schizophrenia rat model that displayed memory impairment and reduced depression in a rat olfactory bulbectomy model. In this study, we investigated the effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on brain neurotransmitter levels and brain neurochemistry in a schizophrenia rat model. Materials and Methods: We administered AKH/RPCH peptides for 4 days sub-chronically, both in naive rats and also in the MK-801-induced schizophrenia rat model. Liquid chromatography-mass spectrometry apparatus was used for targeted and untargeted analysis of rat neurochemistry. Results: Increased brain glutamate levels characteristic of MK-801 peptide-treated rats were significantly reduced by AKH. Furthermore, AKH also increased brain dopamine levels in both naive and MK-801 rats. Metabolomic studies have shown that AKH affects lipid and glutamate metabolism, while hypertrehalosaemic hormone plays a role in sugar metabolism and inflammation. Conclusion: According to our results, AKH might affect dopaminergic and glutamatergic systems and reverse the effects of MK-801, possibly affecting NMDA receptors.

The contributions of neonatal inhalation of copper to air pollution-induced neurodevelopmental outcomes in mice

Exposures to ambient ultrafine particle (UFP) air pollution (AP) during the early postnatal period in mice (equivalent to human third trimester brain development) produce male-biased changes in brain structure, including ventriculomegaly, reduced brain myelination, alterations in neurotransmitters and glial activation, as well as impulsive-like behavioral characteristics, all of which are also features characteristic of male-biased neurodevelopmental disorders (NDDs). The purpose of this study was to ascertain the extent to which inhaled Cu, a common contaminant of AP that is also dysregulated across multiple NDDs, might contribute to these phenotypes. For this purpose, C57BL/6J mice were exposed from postnatal days 4–7 and 10–13 for 4 hr/day to inhaled copper oxide (CuxOy) nanoparticles at an environmentally relevant concentration averaging 171.9 ng/m3. Changes in brain metal homeostasis and neurotransmitter levels were determined following termination of exposure (postnatal day 14), while behavioral changes were assessed in adulthood. CuxOy inhalation modified cortical metal homeostasis and produced male-biased disruption of striatal neurotransmitters, with marked increases in dopaminergic function, as well as excitatory/inhibitory imbalance and reductions in serotonergic function. Impulsive-like behaviors in a fixed ratio (FR) waiting-for-reward schedule and a fixed interval (FI) schedule of food reward occurred in both sexes, but more prominently in males, effects which could not be attributed to altered locomotor activity or short-term memory. Inhaled Cu as from AP exposures, at environmentally relevant levels experienced during development, may contribute to impaired brain function, as shown by its ability to disrupt brain metal homeostasis and striatal neurotransmission. In addition, its ability to evoke impulsive-like behavior, particularly in male offspring, may be related to striatal dopaminergic dysfunction that is known to mediate such behaviors. As such, regulation of air Cu levels may be protective of public health.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of invivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of invivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

Effect of perinatal dietary protein deficiency on some neurochemicals and cytoarchitectural balance, in F1 and F2 generations of rats

ABSTRACT Protein deficiency, characterized by an inadequate intake of protein in the diet that fails to meet the body’s physiological requirements across various stages, can lead to detrimental outcomes. This is of interest due to the persistent low protein content in staple foods and suboptimal dietary patterns. The study sought to assess the intergenerational repercussions of dietary protein deficiency on specific neurochemicals and the cytoarchitecture of the brain within the F1 and F2 generations of rats. The rats were categorized into four groups based on the protein content percentage in their diets: 21% protein diet (21%PD), 10% protein diet (10%PD), 5% protein diet (5%PD), and control diet. Neurobehavior was assessed, while brain serotonin and dopamine levels were measured using HPLC. BDNF and GDNF expression in the hippocampal and prefrontal (PFC) sections, Immunohistochemical investigations of the morphological impact on the hippocampus and PFC, were also analyzed. The protein-deficient groups displayed anxiety, loss of striatal serotonin and increased dopamine levels, degenerated pyramidal cells in the hippocampus, and a prominent reduction in cellular density in the PFC. BDNF and GDNF levels in the PFC were reduced in the 5%PD group. GFAP astrocyte expression was observed to be increased in the prefrontal cortex (PFC) and hippocampal sections, indicating heightened reactivity. The density of hypertrophied cells across generations further suggests the presence of neuroinflammation. Changes in brain structure, neurotransmitter levels, and neurotrophic factor levels may indicate intergenerational alterations in critical regions, potentially serving as indicators of the brain’s adaptive response to address protein deficiency across successive generations.

Diazepam at environmentally relevant concentrations disturbed social interactions and brain neurotransmitters in adult Japanese medaka (Oryzias latipes)

Pollution by diazepam (DZP) is increasingly recognized as a major threat to aquatic organisms, but knowledge about its potential risk to fish is still limited. In this study, we exposed female and male Japanese medaka (Oryzias latipes) to environmentally relevant DZP (0.8 and 8 µg/L) for 28 days and investigated variation in their behavior (on days 7, 14, and 28) and brain neurotransmitter levels (on day 28). The results showed that DZP could be accumulated in the brain and gonads in Japanese medaka. When two fish of the same sex were placed in an aquarium, DZP exposure exhibited typical sedative effects on females (on day 7) and males (on days 7 and 14). However, these sedative effects on both sexes were no longer present after 28 days of exposure. Exposure to DZP induced sex-specific impacts on the social interactions of medaka on days 7, 14, and 28 of exposure in a time-dependent manner. When both sexes were placed into an aquarium in a ratio of 1:1, DZP could significantly alter their locomotor activity and social interaction on days 14 and 28 of the exposure. After 28 days of exposure, DZP significantly altered the levels of several neurotransmitters in the brain of medaka, also in sex-specific manners. The alterations in dopamine and serotonin levels exhibited significant correlations with the increased social interaction between females. At the same time, that of γ-aminobutyric acid significantly correlated to the decreased social interaction between males. Our findings suggest that chronic exposure to DZP, even at environmentally relevant concentrations, can accumulate in the brains and gonads of fish, and alter their behaviors by mediating brain neurotransmitter levels, which may further disturb their reproduction and population dynamics.

Non-invasive invivo measurements of metabolic alterations in the type 2 diabetic brain by 1H magnetic resonance spectroscopy.

Type 2 diabetes (T2D) is a complex chronic metabolic disorder characterized by hyperglycemia because of insulin resistance. Diabetes with chronic hyperglycemia may alter brain metabolism, including brain glucose and neurotransmitter levels; however, detailed, longitudinal studies of metabolic alterations in T2D are lacking. To shed insight, here, we characterized the consequences of poorly controlled hyperglycemia on neurochemical profiles that reflect metabolic alterations of the brain in both humans and animal models of T2D. Using invivo 1H magnetic resonance spectroscopy, we quantified 12 metabolites cross-sectionally in T2D patients and 20 metabolites longitudinally in T2D db/db mice versus db+ controls. We found significantly elevated brain glucose (91%, p < 0.001), taurine (22%, p = 0.02), glucose+taurine (56%, p < 0.001), myo-inositol (12%, p = 0.02), and choline-containing compounds (10%, p = 0.01) in T2D patients versus age- and sex-matched controls, findings consistent with measures in T2D db/db versus control db+ littermates. In mice, hippocampal and striatal neurochemical alterations in brain glucose, ascorbate, creatine, phosphocreatine, γ-aminobutyric acid, glutamate, glutamine, glutathione, glycerophosphoryl-choline, lactate, myo-inositol, and taurine persisted in db/db mice with chronic disease progression from 16 to 48 weeks of age, which were distinct from control db+ mice. Overall, our study demonstrates the utility of 1H magnetic resonance spectroscopy as a non-invasive tool for characterizing and monitoring brain metabolic changes with T2D progression.

Effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African Sharptooth Catfish Clarias gariepinus.

The study investigated the effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African Sharptooth Catfish Clarias gariepinus. Juveniles were exposed to different concentrations of haloperidol (0.12, 0.24, and 0.48 mg/L) for 15 days and subsequently withdrawn from the drug for 5 days. Blood samples from the fish on days 1, 5, 10, and 15 and after the 5-day withdrawal period were analyzed for mutagenic changes, after which the fish were sacrificed. The brain was sampled for serotonergic and dopaminergic analyses. There was formation of micronuclei in the peripheral fish blood, which increased as the duration and concentrations of the drug increased. The drug significantly reduced the serotonin activity but increased dopamine activity. Some of the studied parameters, however, recovered from the effects of the drug after the 5-day withdrawal period. Haloperidol is toxic to fish, and its use in the environment should be guarded to avoid adverse impacts on nontarget species like fish.

Prepubertal Continuous Dietary Folate Fortification Enhances the Brain Function of Adult Mice by Modulating Antioxidant Status, Inflammation, and Brain Neurotransmitter Levels.

The benefits of folic acid supplementation have been documented in several studies. However, while evidence exists regarding its benefits for growth and haematologic parameters, its possible effects on the brain have been less examined. The study aimed to examine the benefits of dietary folic acid supplementation (beginning in the prepubertal period) on neurobehaviour, oxidative stress, inflammatory parameters, and neurotransmitter levels in adult mice. Forty-eight prepubertal male mice were assigned into four groups of 12 animals each. Mice were grouped into normal control (fed standard diet) and three groups fed folic acid supplemented diet at 2.5, 5, and 10 mg/kg of feed. Animals were fed a standard diet or folic acid-supplemented diet for eight weeks during which food intake and body weight were assessed. On postnatal day 78, animals were exposed to the open-field, Y-maze, radial arm maze, elevated plus maze, bar test, and models of behavioural despair. 24 hours after the last behavioural test, animals were made to fast overnight and then sacrificed by cervical dislocation. Blood was then taken for the assessment of blood glucose, leptin, and insulin levels. Homogenates of brain tissue were prepared and used for the assessment of biochemical parameters. Results showed a concentration-dependent increase in body weight, and improved antioxidant status, memory scores, and acetylcholine levels. Also, a decrease in food intake, blood glucose, insulin, and leptin levels was observed. A reduction in open-field behaviour, anxiety-related behaviour, and proinflammatory markers, was also observed. The beneficial effect of prepubertal continuous dietary folate fortification on the brain (as the animal ages) has been shown in this study.

Changes in neurotransmitter levels, brain structural characteristics, and their correlation with PANSS scores in patients with first-episode schizophrenia.

In patients with schizophrenia, the brain structure and neurotransmitter levels change, which may be related to the occurrence and progression of this disease. To explore the relationships between changes in neurotransmitters, brain structural characteristics, and the scores of the Positive and Negative Symptom Scale (PANSS) in patients with first-episode schizophrenia. The case group comprised 97 patients with schizophrenia, who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022. The control group comprised 100 healthy participants. For all participants, brain structural characteristics were explored by measuring brain dopamine (DA), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) levels, with magnetic resonance imaging. The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis. Linear correlation analysis was used to analyze the correlations between neurotransmitters, brain structural characteristics, and PANSS scores. Patients in the case group had higher levels of DA and lower levels of Glu and GABA, greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group (P < 0.05). Patients with positive schizophrenia symptoms had significantly higher levels of DA, Glu, and GABA than those with negative symptoms (P < 0.05). In patients with positive schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical and horizontal distances between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). In patients with negative schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical distance between the corpus callosum and the infrafornix, horizontal distance between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). In patients with first-episode schizophrenia, DA levels increased, Glu and GABA levels decreased, the thickness of the corpus callosum increased, and these variables were correlated with PANSS scores.

Neonatal bilateral whisker trimming in male mice age-dependently alters brain neurotransmitter levels and causes adolescent onsets of social behavior abnormalities.

Tactile perception via whiskers is important in rodent behavior. Whisker trimming during the neonatal period affects mouse behaviors related to both whisker-based tactile cognition and social performance. However, the molecular basis of these phenomena is not completely understood. To solve this issue, we investigated developmental changes in transmitters and metabolites in various brain regions of male mice subjected to bilateral whisker trimming during the neonatal period (10 days after birth [BWT10 mice]). We discovered significantly lower levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), the major noradrenaline metabolite, in various brain regions of male BWT10 mice at both early/late adolescent stages (at P4W and P8W). However, reduced levels of dopamine (DA) and their metabolites were more significantly identified at P8W in the nuclear origins of monoamine (midbrain and medulla oblongata) and the limbic system (frontal cortex, amygdala, and hippocampus) than at P4W. Furthermore, the onset of social behavior deficits (P6W) was observed later to the impairment of whisker-based tactile cognitive behaviors (P4W). Taken together, these findings suggest that whisker-mediated tactile cognition may contribute toprogressive abnormalities in social behaviors in BWT10 mice accompanied by impaired development of dopaminergic systems.

Fructo-oligofructose ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions and psychiatric comorbidities in mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus and eczema lesions and psychiatric comorbidities. The gut-brain-skin axis plays a pivotal role during AD development, which might suggest a novel therapeutic strategy for AD. The present study aims to uncover the protective effects and underlying mechanisms of fructo-oligofructose (FOS), a type of prebiotic, on AD-like skin manifestations and comorbid anxiety and depression in AD mice. Female Kunming mice were treated topically with 2,4-dinitrofluorobenzene (DNFB) to induce AD-like symptoms and FOS was administered daily for 14 days. The results showed that FOS could alleviate AD-like skin lesions markedly as evidenced by dramatic decreases in severity score, scratching bouts, the levels of immunoglobulin E (IgE) and T helper 1(Th1)/Th2-related cytokines, and the infiltration of inflammatory cells and mast cells to the dermal tissues. The comorbid anxiety and depressive-like behaviors, estimated by the forced swimming test (FST), the tail-suspension test (TST), the open-field test (OFT), and the zero maze test (ZMT) in AD mice, were significantly attenuated by FOS. Fructo-oligofructose significantly upregulated brain neurotransmitters levels of 5-hydroxytryptamine (5-HT) and dopamine (DA). Furthermore, FOS treatment increased the relative abundance of gut microbiota, such as Prevotella and Lactobacillus and the concentrations of short-chain fatty acids (SCFAs), especially acetate and iso-butyrate in the feces of AD mice. The correlation analysis indicated that the reshaped gut microbiome composition and enhanced SCFAs formation are associated with skin inflammation and behavioral alteration. Collectively, these data identify FOS as a promising microbiota-targeted treatment for AD-like skin inflammation and comorbid anxiety and depressive-like behaviors. © 2023 Society of Chemical Industry.

Postoperative delirium: identifying the patient at risk and altering the course

Postoperative delirium (POD) is a common neurocognitive syndrome seen in older patients after major surgery. POD is linked to longer stays in hospital and intensive care, a greater incidence of postoperative complications, worse functional outcome, and higher mortality. Researchers have not yet fully elucidated the exact pathophysiology of POD. Several risk factors that contribute to the development of POD have been identified, such as advanced age, cardiac or hip surgery, preoperative cognitive decline or delirium, disturbances in brain levels of neurotransmitters and information processing, oxidative stress and neuro-inflammation. Identifying patients at risk for POD enables a more precise and efficient allocation of medical resources and facilitates POD prevention and management. The present review addresses how to identify patients at risk of POD and summarizes the currently available evidence and best-practice recommendations for peri-operative management and prevention of POD.