Impairment In Animals Research Articles

Impact of subclinical mastitis on greenhouse gas emissions intensity and profitability of dairy cows in Norway

Impaired animal health causes both productivity and profitability losses on dairy farms, resulting in inefficient use of inputs and increase in greenhouse gas (GHG) emissions produced per unit of product (i.e. emissions intensity). Here, we used subclinical mastitis as an exemplar to benchmark alternative scenarios against an economic optimum and adjusted herd structure to estimate the GHG emissions intensity associated with varying levels of disease. Five levels of somatic cell count (SCC) classes were considered namely 50,000 (i.e. SCC50), 200,000, 400,000, 600,000 and 800,000cells/mL (milliliter) of milk. The effects of varying levels of SCC on milk yield reduction and consequential milk price penalties were used in a dynamic programming (DP) model that maximizes the profit per cow, represented as expected net present value, by choosing optimal animal replacement rates. The GHG emissions intensities associated with different levels of SCC were then computed using a farm-scale model (HolosNor). The total culling rates of both primiparous (PP) and multiparous (MP) cows for the five levels of SCC scenarios estimated by the model varied from a minimum of 30.9% to a maximum of 43.7%. The expected profit was the highest for cows with SCC200 due to declining margin over feed, which influenced the DP model to cull and replace more animals and generate higher profit under this scenario compared to SCC50. The GHG emission intensities for the PP and MP cows with SCC50 were 1.01kg (kilogram) and 0.95kg carbon dioxide equivalents (CO2e) per kg fat and protein corrected milk (FPCM), respectively, with the lowest emissions being achieved in SCC50. Our results show that there is a potential to reduce the farm GHG emissions intensity by 3.7% if the milk production was improved through reducing the level of SCC to 50,000cells/mL in relation to SCC level 800,000cells/mL. It was concluded that preventing and/or controlling subclinical mastitis consequently reduces the GHG emissions per unit of product on farm that results in improved profits for the farmers through reductions in milk losses, optimum culling rate and reduced feed and other variable costs. We suggest that further studies exploring the impact of a combination of diseases on emissions intensity are warranted.

Overtraining modifies spatial memory susceptibility to corticosterone administration

Even though the effects of overtraining and glucocorticoids on different phases of spatial memory are known, the interaction between these factors on the retrieval and extinction of spatial memory has not yet been described. Adult male Wistar rats received eight training trials per day in the Barnes maze for either one or two days. Twenty-four hours after the last training trial they were randomly assigned for receiving an intraperitoneal vehicle or corticosterone injection (0.125 or 0.5 mg/kg) and ten minutes later they were given a memory test, followed by seven extinction trials. Extinction retention was evaluated twenty-four hours after extinction. The second training session did not provoke significant changes regarding escape latency nor weighted errors, thereby showing that overtraining had been obtained. The overtrained animals performed better than the trained ones during the retrieval test. Corticosterone administration did not affect the overtrained animals’ performance; by contrast, only the lower dose impaired trained animals’ retrieval. Overtrained subjects acquired extinction more rapidly than those which received just one session, but corticosterone did not significantly modify extinction. However, whilst the spatial task remained extinguished in trained animals during the extinction retrieval test, spontaneous recovery occurred in overtrained animals. Such training intensity effects on extinction retrieval were reverted by corticosterone. Overall, these results suggested that overtraining modified the susceptibility of spatial memory’s trace to the effects of corticosterone on retrieval and extinction.

The extent of intrauterine growth restriction determines the severity of cerebral injury and neurobehavioural deficits in rodents.

BackgroundCerebral Palsy (CP) is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a) reflect the heterogeneity of the condition and b) can be used to evaluate new translational therapies. To address these key knowledge gaps, we characterized a chronic placental insufficiency (PI) model, using bilateral uterine artery ligation (BUAL) of dams. This injury model results in intrauterine growth restriction (IUGR) in pups, and animals recapitulate the human phenotype both in terms of neurobehavioural and anatomical deficits.MethodsEffects of BUAL were studied using luxol fast blue (LFB)/hematoxylin & eosin (H&E) staining, immunohistochemistry, quantitative Magnetic Resonance Imaging (MRI), and Catwalk neurobehavioural tests.ResultsNeuroanatomical analysis revealed regional ventricular enlargement and corpus callosum thinning in IUGR animals, which was correlated with the extent of growth restriction. Olig2 staining revealed reductions in oligodendrocyte density in white and grey matter structures, including the corpus callosum, optic chiasm, and nucleus accumbens. The caudate nucleus, along with other brain structures such as the optic chiasm, internal capsule, septofimbrial and lateral septal nuclei, exhibited reduced size in animals with IUGR. The size of the pretectal nucleus was reduced only in moderately injured animals. MAG/NF200 staining demonstrated reduced myelination and axonal counts in the corpus callosum of IUGR animals. NeuN staining revealed changes in neuronal density in the hippocampus and in the thickness of hippocampal CA2 and CA3 regions. Diffusion weighted imaging (DWI) revealed regional white and grey matter changes at 3 weeks of age. Furthermore, neurobehavioural testing demonstrated neuromotor impairments in animals with IUGR in paw intensities, swing speed, relative print positions, and phase dispersions.ConclusionsWe have characterized a rodent model of IUGR and have demonstrated that the neuroanatomical and neurobehavioural deficits mirror the severity of the IUGR injury. This model has the potential to be applied to examine the pathobiology of and potential therapeutic strategies for IUGR-related brain injury. Thus, this work has potential translational relevance for the study of CP.

Impairment of neural coordination in hippocampal neuronal ensembles after a psychotomimetic dose of dizocilpine

The discoordination hypothesis of schizophrenia posits discoordination of neural activity as the central mechanism that underlies some psychotic symptoms (including ‘hallmark’ cognitive symptoms) of schizophrenia. To test this proposition, we studied the activity of hippocampal neurons in urethane anesthetized Long Evans rats after 0.15mg/kg dizocilpine (MK-801), an N-Methyl-d-aspartate (NMDA) glutamate receptor antagonist, which can cause psychotic symptoms in humans and cognitive control impairments in animals. We observed that MK-801 altered the temporal coordination, but not rate, of neuronal firing. Coactivation between neurons increased, driven primarily by increased coincident firing of cell pairs that did not originally fire together before MK-801 injection. Increased pairwise coactivation manifested as disorganized discharge on the level of neuronal ensembles, which in turn could lead to disorganization in information processing. Disorganization of neuronal activity after a psychotomimetic dose of MK-801 supports the discoordination hypothesis of psychosis.

Short communication: Supplementation of fructo-oligosaccharides does not improve insulin sensitivity in heavy veal calves fed different sources of carbohydrates

Heavy veal calves (4-6 mo old) often develop problems with insulin sensitivity. This could lead to metabolic disorders and impaired animal growth performance. Studies in various animal species have shown that the supplementation of short-chain fructo-oligosaccharides (scFOS) can improve insulin sensitivity. We therefore studied the effects of scFOS supplementation on insulin sensitivity in heavy veal calves. Forty male Holstein-Friesian calves (BW = 190 ± 2.9 kg; age = 162 ± 1.4 d at the start of the trial) were fed either a control milk replacer (MR) diet or a diet in which one-third of the lactose was replaced by glucose, fructose, or glycerol for 10 wk prior to the start of the trial. At the start of the trial, calves were subjected to a frequently sampled intravenous glucose tolerance test to assess whole-body insulin sensitivity (muscle and hepatic insulin sensitivity). Calves within each dietary treatment group were ranked based on their insulin sensitivity value. Half of the calves received scFOS (12 mg/kg of BW) with the MR for 6 wk (supplementation was equally distributed over the insulin sensitivity range). Subsequently, a second frequently sampled intravenous glucose tolerance test was conducted to assess the effect of scFOS. In addition, fasting plasma levels of glucose, insulin, triglycerides, and cholesterol were determined to calculate the quantitative insulin sensitivity check index and triglyceride:high-density lipoprotein cholesterol ratio (fasting indicators of insulin sensitivity). Whole-body insulin sensitivity was low at the start of the trial and remained low in all groups [1.0 ± 0.1 and 0.8 ± 0.1 (mU/L)-1 · min-1 on average, respectively]. Supplementation of scFOS did not improve insulin sensitivity in any of the treatment groups. The quantitative insulin sensitivity check index and the triglyceride:high-density lipoprotein cholesterol ratio also did not differ between scFOS and non-scFOS calves and averaged 0.326 ± 0.003 and 0.088 ± 0.004, respectively, at the end of the trial. We conclude that scFOS supplementation does not improve insulin sensitivity in heavy veal calves regardless of the carbohydrate composition of the MR. This is in contrast to other animals (e.g., dogs and horses), where scFOS supplementation did improve insulin sensitivity. The absence of an effect of scFOS might be related to the dosage or to metabolic differences between ruminants and nonruminants. Increasing evidence indicates that dietary interventions in veal calves have little or no effect on insulin sensitivity, possibly because of low levels of insulin sensitivity.

Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy.

Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10-30 pN alterations in RasBRaf intermolecular binding force. The magnitude of changes in RasBRaf binding force correlates with the size of alterations in protein affinity and in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptor (-R)-mediated synaptic transmission in neurons expressing replacement BRaf mutants, and predicts the extent of learning impairments in animals expressing replacement BRaf mutants. These results establish single-molecule force spectroscopy as an effective platform for evaluating the piconewton-level interaction of signaling molecules and predicting the behavior outcome of signal transduction.

Are conflict-causing tigers different? Another perspective for understanding human-tiger conflict in Chitwan National Park, Nepal

We analyzed characteristics of the problem-causing tigers in Chitwan National Park (Nepal) to determine if specific groups or individuals in the source population have higher probability to get involved in conflicts with humans. From 2007 to 2016 we identified a total of 22 such tigers including 13 that killed humans, six serial livestock killers and three tigers that threatened human safety (with no reported human and livestock casualty). Thirteen of these tigers were controlled or killed and four were relocated. We compared a subset of 15 ‘problem tigers’ involved in conflict between 2009 and 2013 with the Chitwan's tiger population obtained from three different sessions of camera trapping (2009, 2010 and 2013). We found that <5% of this source population (tigers recorded in camera trap) were involved in conflict. We conclude that transient tigers without a territory or physically impaired animals are more likely to be involved in conflict and recommend an early warning system be adopted to anticipate conflicts before they occur. This system should include regular monitoring and timely identification of problem tigers followed by decisive management action to either remove the tiger or encourage local people to modify their behavior to reduce the risk of conflict.

Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota.

Subclinical chronic inflammation (SCI) is associated with impaired animal growth. Previous work has demonstrated that olive-derived plant bioactives exhibit anti-inflammatory properties that could possibly counteract the growth-depressing effects of SCI. To test this hypothesis and define the underlying mechanism, we conducted a 30-day study in which piglets fed an olive-oil bioactive extract (OBE) and their control counterparts (C+) were injected repeatedly during the last 10 days of the study with increasing doses of Escherichia coli lipopolysaccharides (LPS) to induce SCI. A third group of piglets remained untreated throughout the study and served as a negative control (C-). In C+ pigs, SCI increased the circulating concentration of interleukin 1 beta (p < 0.001) and decreased feed ingestion (p < 0.05) and weight gain (p < 0.05). These responses were not observed in OBE animals. Although intestinal inflammation and colonic microbial ecology was not altered by treatments, OBE enhanced ileal mRNA abundance of tight and adherens junctional proteins (p < 0.05) and plasma recovery of mannitol (p < 0.05) compared with C+ and C-. In line with these findings, OBE improved transepithelial electrical resistance (p < 0.01) in TNF-α-challenged Caco-2/TC-7 cells, and repressed the production of inflammatory cytokines (p < 0.05) in LPS-stimulated macrophages. In summary, this work demonstrates that OBE attenuates the suppressing effect of SCI on animal growth through a mechanism that appears to involve improvements in intestinal integrity unrelated to alterations in gut microbial ecology and function.

Association of claw disorders with subclinical intramammary infections in Egyptian dairy cows.

Aim:Bovine mastitis and lameness are the most common production diseases affecting dairy farms worldwide resulting in huge economic impact and impaired animal welfare. The objective of this field study was to investigate the association of infectious and non-infectious claw disorders with the occurrence of subclinical intramammary infections (IMIs) diagnosed by California mastitis test (CMT) in dairy cows under Egyptian conditions.Materials and Methods:A total of 43 dairy cows were included in this field study. Subclinical IMI was diagnosed by CMT on all lactating quarters of cows. A cow was considered to have subclinical IMI if it had at least one subclinically infected quarter (≥3). Cows were inspected carefully for claw disorders that recorded based on type and site. Locomotion and body condition scores were also recorded for each cow in addition to the limb affected. The association between the CMT and other explanatory variables was tested by Fisher’s exact test.Results:The prevalence of infectious and non-infectious claw disorders was 81.4% (35/43) and 32.6% (14/43), respectively. Digital dermatitis (DD) and heel horn erosion were the most prevalent infectious type with 79% (34/43) and 58% (25/43), respectively, while wall fissure was the most identified non-infectious one 11.6% (5/43). The prevalence of claw disorders in hind limbs was 88.4% (38/43) and 11.6% (5/43) in the forelimbs. Infectious claw disorders were significantly associated with the subclinical IMI diagnosed by CMT (p<0.05). Non-infectious claw affections, locomotion score, body condition score, and the affected limb had no association with the occurrence of subclinical IMI.Conclusion:DD is the highest prevalent claw disorder observed in dairy cows in Egypt. The hind limbs are more susceptible to claw disorders than the forelimbs. Infectious type of claw disorders is significantly associated with subclinical IMI diagnosed by CMT in dairy cows under Egyptian conditions indicating that the infectious types of claw affections may influence the udder health.

Caffeine alleviates progressive motor deficits in a transgenic mouse model of spinocerebellar ataxia.

Machado-Joseph disease (MJD) is a neurodegenerative spinocerebellar ataxia (SCA) associated with an expanded polyglutamine tract within ataxin-3 for which there is currently no available therapy. We previously showed that caffeine, a nonselective adenosine receptor antagonist, delays the appearance of striatal damage resulting from expression of full-length mutant ataxin-3. Here we investigated the ability of caffeine to alleviate behavioral deficits and cerebellar neuropathology in transgenic mice with a severe ataxia resulting from expression of a truncated fragment of polyglutamine-expanded ataxin-3 in Purkinje cells. Control and transgenic c57Bl6 mice expressing in the mouse cerebella a truncated form of human ataxin-3 with 69 glutamine repeats were allowed to freely drink water or caffeinated water (1g/L). Treatments began at 7 weeks of age, when motor and ataxic phenotype emerges in MJD mice, and lasted up to 20 weeks. Mice were tested in a panel of locomotor behavioral paradigms, namely rotarod, beam balance and walking, pole, and water maze cued-platform version tests, and then sacrificed for cerebellar histology. Caffeine consumption attenuated the progressive loss of general and fine-tuned motor function, balance, and grip strength, in parallel with preservation of cerebellar morphology through decreasing the loss of Purkinje neurons and the thinning of the molecular layer in different folia. Caffeine also rescued the putative striatal-dependent executive and cognitive deficiencies in MJD mice. Our findings provide the first in vivo demonstration that caffeine intake alleviates behavioral disabilities in a severely impaired animal model of SCA. Ann Neurol 2017;81:407-418.

Possible involvement of the CA1 GABAergic system on harmaline induced memory consolidation deficit.

Activation of the GABAB receptors inhibit learning and memory processes. The current research was designed to examine the role of dorsal hippocampal (CA1) GABAB receptors on harmaline induced memory consolidation deficit in mice. For this purpose, the effects induced by the GABAB antagonist phaclofen and the GABAB agonist baclofen on memory consolidation were assessed by using the step-down inhibitory avoidance task. Furthermore, the possible involvement of harmaline on GABAB receptor's effects was also assessed through using the same behavioral procedure. In a first dose response experiments, post-training intra-CA1 injections of phaclofen did not change while baclofen (0.1μg/mouse) impaired animals' performance in this task, suggesting a modulation of storage of information. Moreover, Post-training intra-peritoneal (i.p.) infusion of harmaline (2 and 5mg/kg) also decreased memory consolidation. Interestingly, phaclofen at the sub-threshold dose (0.001μg/mouse, intra-CA1), successfully antagonized the deficits on memory consolidation induced by the highest doses of harmaline (2 and 4mg/kg, i.p.). On the other hand, non significant dose of baclofenc (0.001μg/mouse, intra-CA1) potentiated impairment of memory consolidation induced by harmaline (2mg/kg, i.p.). In addition in all experiments, locomotor activity did not alter significantly. These results indicate a) that the CA1 GABAB receptors are involved in memory consolidation b) that harmaline interact with the CA1 GABAB receptors in modulation of memory consolidation.

Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging

Sleep-disordered breathing produces cognitive impairments, and is possibly associated with Alzheimer disease (AD). Intermittent hypoxia treatment (IHT), an experimental model for sleep-disordered breathing, results in cognitive impairments in animals via unknown mechanisms. Here, we exposed mice to IHT protocols, and performed biochemical analyses and microarray analyses regarding their hippocampal samples. In particular, we performed gene ontology (GO)-based microarray analysis to elucidate effects of IHT on hippocampal functioning, which were compared with the effects of various previously-reported experimental conditions on that (ref. Gene Expression Omnibus, The National Center for Biotechnology Information). Our microarray analyses revealed that IHT and aging shared alterations in some common GO, which were also observed with kainic acid treatment, Dicer ablation, or moderate glutamate excess. Mapping the altered genes using the Kyoto Encyclopedia of Genes and Genomes PATHWAY database indicated that IHT and aging affected several pathways including “MAPK signaling pathway”, “PI3K-Akt signaling pathway”, and “glutamatergic synapse”. Consistent with the gene analyses, in vivo analyses revealed that IHT increased phosphorylated tau, reflecting an imbalance of kinases and/or phosphatases, and reduced proteins relevant to glutamatergic synapses. In addition, IHT increased phosphorylated p70 S6 kinase, indicating involvement of the mammalian target of rapamycin signaling pathway. Furthermore, IHT mice demonstrated hyperactivity in Y-maze tests, which was also observed in AD models. We obtained important data or something from the massive amount of microarray data, and confirmed the validity by in vivo analyses: the IHT-induced cognitive impairment may be partially explained by the fact that IHT increases phosphorylated tau via biological processes common to aging. Moreover, as aging is a major risk factor for AD, IHT is a novel model for investigating the pathological processes contributing to AD onset.

Effects of early neonatal proinflammatory stress on the expression of BDNF transcripts in the brain regions of prepubertal male rats

Early postnatal proinflammatory stress may evoke behavioral impairments in adulthood; however, the underlying mechanisms are still elusive. The brain-derived neurotrophic factor (BDNF) plays a key role in neuroplastic changes in health, as well as in pathology. The BDNF gene is transcribed to exon-specific mRNAs and the pattern of their expression depends on stimulus. We suggested that disturbances of the exonspecific BDNF mRNA expression in the brain regions after stress induced by proinflammatory stimuli in the early postnatal period could be one of the underlying mechanisms of consequent behavioral impairments. Thus, the aim of the study was to examine the effects of proinflammatory stress in early postnatal ontogeny on the BDNF polypeptide content and the patterns of expression of the BDNF gene in the neocortex and hippocampus of prepubertal male rats. The proinflammatory stress was induced by the subcutaneous administration of bacterial lipopolysaccharide (LPS) to rat pups on postnatal days 3 and 5, while BDNF expression was studied in 36-day-old rats. The BDNF polypeptide content was estimated using an enzyme-linked immunosorbent assay, while a quantitative polymerase chain reaction followed by reverse transcription was used to detect the exon-specific BDNF mRNA expression. The levels of BDNF and its transcripts, containing the common exon IX were similar in the control and LPS-treated rats. In the rats treated with LPS, the level of BDNF mRNA containing exon IV was lower in the neocortex but not in the hippocampus. No changes in the expression of the transcripts containing exons I and VI were observed in any of the brain structures studied. We suggest that specific alterations in BDNF expression may be involved in susceptibility to the development of behavioral impairments of animals subjected to early proinflammatory stress.

Experience of experimental modelling of Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by choreic involuntary movements, decline in cognitive functions, behavioral disturbances, and progressive neuronal death affecting primarily the striatum. The fatal nature of HD makes it important to search for new effective methods of its treatment, which requires the development of experimental models of the disease. These models can be created using 3-nitropropionic acid (3-NPA), which is a neurotoxin causing typical changes in motor skills and memory impairment in animals due to induction of oxidative stress, impaired glutathione defense, and destruction of striatal cells. We modeled HD in rats by chronic daily intraperitoneal administration of 3-NPA for 17 days. Systemic administration of a low dose of 3-NPA (10 mg/kg) induced hyperactivity of animals in the open field test (including movement redundancy as a hyperkinesia analogue) and had no effect on the behavior of the animals in the X-maze test. On the contrary, rats administered with a toxic dose of 3-NPA (20 mg/kg) exhibited a significant decrease in their motor activity and a cognitive decline in behavioral tests. A histopathological analysis revealed damage and loss of neurons and a decrease in expression of dopaminergic markers (tyrosine hydroxylase and plasma membrane dopamine transporter) in the striatum. The gliotoxic effect of 3-NPA was also found in the striatum, which was confirmed by immunohistochemical staining for astrocytic proteins: GFAP, glutamine synthetase, and aquaporin-4. This HD model may be helpful for testing new experimental therapies at different stages of HD-like neurodegeneration, including therapies based on cell neurotransplantation.

Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves.

In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10-2 [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that increasing the contribution of fat to the digestible energy intake from the MR from 20 to 50%, at the expense of lactose does not affect whole-body insulin sensitivity and insulin secretion in calves. However, a high-lactose MR increases postprandial glucose and insulin responses, whereas a high-fat MR increases fat accumulation in liver but not muscle.

Parkinson's Disease, Diabetes and Cognitive Impairment.

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Elimination of virulent strains (aprV2) of Dichelobacter nodosus from feet of 28 Swiss sheep flocks: A proof of concept study

Virulent ovine footrot caused by Dichelobacter nodosus is an endemic disease worldwide. It is associated with severe pain, impaired animal welfare and economic losses. The competitive real-time PCR for the differentiation of virulent aprV2 and benign aprB2 strains of Dichelobacter nodosus provides an objective, rapid and sensitive diagnostic tool for footrot surveillance, especially as it enables early detection of subclinical carriers of virulent strains. The aim of this study was to evaluate the feasibility of complete elimination of Dichelobacter nodosus strains carrying the aprV2 gene from sheep flocks. The treatment protocol was based on careful removal of loose and severely overgrown claw horn, weekly stand-in foot baths of the entire flock for 10 min per sheep, using a 10% zinc sulphate disinfectant solution, clinical and PCR follow-up and isolation or culling of non-responders.Dichelobacter nodosus strains carrying the aprV2 gene were successfully eliminated from the feet of the sheep of all 28 flocks (100%) participating in the study within 6–19 weeks of weekly foot bathing. A strong correlation between the length of time for weekly foot bathing to eliminate the virulent strains and the within-flock prevalence of clinical footrot at the beginning was observed (rho, 0.68; P < 0.001). A statistically significant correlation was not detected between flock size and the length of time for weekly foot bathing (rho, 0.28; P = 0.14), or the prevalence of clinical footrot at study commencement (rho, −0.04; P = 0.82), respectively. In conclusion, a complete elimination of Dichelobacter nodosus strains carrying the aprV2 gene in sheep flocks was possible with a protocol based on careful trimming, weekly stand-in foot baths, and identification of infection using a specific PCR-test and isolation or culling of non-responders.

Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, commonly characterized by altered social behavior, communication, biochemistry and pathological conditions. One percent of the worldwide population suffers from autism and males suffer more than females. NMDA receptors have the important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. This study has been designed to investigate the role of memantine, a NMDA receptor modulator, in prenatal valproic acid-induced autism in rats. Animals with prenatal valproic acid have shown the reduction in social interaction (three-chamber social behavior apparatus), spontaneous alternation (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, prenatal valproic acid-treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood-brain barrier permeability. Treatment with memantine has significantly attenuated prenatal valproic acid-induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, memantine has also attenuated the prenatal valproic acid-induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood-brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behavior, biochemistry and blood-brain barrier impairment in animals, which were significantly attenuated by memantine. NMDA receptor modulators like memantine should be explored further for the therapeutic benefits in autism.

Oscillatory activity in primate reticular formation

Background Piper rhythmicity (35–60 Hz) has been reported in EMGs since 1907. These oscillations are often assumed to originate in the cortex, as they are coherent with sensorimotor EEG (Brown et al., 1998). However, we have recently seen similar oscillations in a slice preparation of primate brainstem reticular formation. These oscillations were decreased by the GABA-A antagonist bicuculline, and completely suppressed by the GAP junction blocker carbenoxolone, suggesting generation by a complex intrinsic network. Given our recent work showing the importance of the reticular formation for recovery after corticospinal tract lesion (Zaaimi et al., 2012); we were interested in whether such oscillations might become more visible during functional recovery. Methods Macaque monkeys were trained to pull a lever, which opened a door allowing them to retrieve a food reward. In two animals, after training we made a unilateral lesion of the pyramidal tract by thermocoagulation, and allowed recovery, which reached plateau after ∼ 4 months. Results The recovery differed between the two lesioned monkeys: one was moderately impaired and could still take the food with the paretic hand, whilst the second lost the ability to perform precision grip but was still able to pull a lever. Recordings were then made of local field potential (LFP) from the reticular formation and EMG. Recordings from one unlesioned animal served as a control. Conclusions In the control and in the less impaired monkeys reticulomuscular coherence was observed in the beta band (20–30 Hz); this was not seen in the more impaired monkey. By contrast, the more impaired animal showed ∼ 70 Hz oscillations in reticular formation LFP around the time of movement. These preliminary results suggest that intrinsic rhythmicity around 40–60 Hz is present in the reticular formation and could be unmasked after lesion of pyramidal tract.

Striatal dynamics explain duration judgments.

The striatum is an input structure of the basal ganglia implicated in several time-dependent functions including reinforcement learning, decision making, and interval timing. To determine whether striatal ensembles drive subjects' judgments of duration, we manipulated and recorded from striatal neurons in rats performing a duration categorization psychophysical task. We found that the dynamics of striatal neurons predicted duration judgments, and that simultaneously recorded ensembles could judge duration as well as the animal. Furthermore, striatal neurons were necessary for duration judgments, as muscimol infusions produced a specific impairment in animals' duration sensitivity. Lastly, we show that time as encoded by striatal populations ran faster or slower when rats judged a duration as longer or shorter, respectively. These results demonstrate that the speed with which striatal population state changes supports the fundamental ability of animals to judge the passage of time.