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Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species.

Mucopolysaccharidosis type IIIA (MPS IIIA) is an inherited metabolic disorder caused by a lysosomal enzyme deficiency resulting in heparan sulphate (HS) accumulation and manifests with a progressive neurodegenerative phenotype. A naturally occurring MPS IIIA mouse model is invaluable for preclinical evaluation of potential treatments but the ability to effectively assess neurological function has proved challenging. Here, the aim was to evaluate a set of behaviour tests for their reliability in assessing disease progression in the MPS IIIA mouse model. Compared to wild-type (WT) mice, MPS IIIA mice displayed memory and learning deficits in the water crossmaze from mid-stage disease and locomotor impairment in the hind-limb gait assessment at late-stage disease, supporting previous findings. Declined wellbeing was also observed in the MPS IIIA mice via burrowing and nest building evaluation at late-stage disease compared to WT mice, mirroring the progressive nature of neurological disease. Excessive HS accumulation observed in the MPS IIIA mouse brain from 1 month of age did not appear to manifest as abnormal behaviours until at least 6 months of age suggesting there may be a threshold of HS accumulation before measurable neurocognitive decline. Results obtained from the open field and three-chamber sociability test are inconsistent with previous studies and do not reflect MPS IIIA patient disease progression, suggesting these assessments are not reliable. In conclusion, water cross-maze, hind-limb gait, nest building and burrowing, are promising assessments in the MPS IIIA mouse model, which produce consistent results that mimic the human disease.

Gliclazide (GLD), a sulphonylurea is efficacious in the treatment of diabetes type-2. However, there is limited information on its activity in the brain, especially in diabetics. This research investigated the brain activities of GLD following streptozotocin-induced diabetes in Wistar rats. Twenty five adult male Wistar rats (200–250 g) were grouped (n = 5) as: Control (distilled water, 5 mL/kg) and GLD (150 mg/kg) groups; and the diabetic groups, untreated streptozotocin (STZ, 35 mg/kg), and STZ (35 mg/kg) treated with GLD (150 mg/kg) for two and four weeks, and already on high fat diet. The animals’ body weights and blood glucose levels were checked weekly. After the experimental duration, spontaneous alternation and novel object recognition tests were carried out and the animals sacrificed. Perfusion with phosphate buffered saline preceded brain excision for biochemical analyses, with halves fixed in 10% neutral buffered formalin for histology. Compared with the control, results showed (p

Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species. • Fish exposed to MPs exhibit neurotoxicity, immunotoxicity, and oxidative stress. • MPs disrupt neurotransmitters in fish, affecting social interactions and cognitive function. • MP exposure disrupts fish hormonal signaling pathways, impacting reproductive function. [ABSTRACT FROM AUTHOR]

The objective designated to discover the analgesic effect of nefopam in the normal (non-stressed) chickens and its possible alteration due to hydrogen peroxide (H2O2)-induced oxidative stress (OS) in 7-14 day old chickens. The analgesia of nefopam has been increased by 47% in the stressed chickens by measuring the analgesic Median Effective Dose (ED50) value. This value was 9.10 mg/kg, IM in the normal chickens where it became 4.80 mg/kg, IM in stressed chickens. There is a significant rise in the antinociceptive action of nefopam 18 mg/kg, IM by 88% in the stressed group of chickens in comparison with the normal one elicited by an electro-stimulation and formaldehyde 0.05 ml of 0.1% tests for induction of nociception. The observations showed several significant stimulatory modifications in the neurobehaviour when nefopam treated with a subtle dosage 1 mg/kg, IM in the stressed chickens concerning the latency to move, squares crossed and time of the tonic immobility response test. Significant damage was detected in the liver function when nefopam injected at 18 mg/kg, IM in stress chickens in comparison to normal one by 28, 33 and 65% as estimated through Alkaline phosphatase (ALP), Aspartate trans-aminase (AST) and Alanine trans-aminase (ALT) concentrations in the serum, respectively. The sum of data findings indicated that H2O2-inducedOS increased the analgesic activity of nefopam in the chickens; despite the changes occur on the neurobehaviour and liver function. The dose of nefopam should be reduced when preparing the therapeutic regimen in the stressed animals.

Mercury (Hg) exposure is known to damage vital components of the central nervous system primarily through oxidative stress. Although Phyllanthus amarus (PA) is reported to be rich in antioxidants, there is a dearth of relevant research evidence to show its protective activity against Mercuric chloride (HgCl2)-induced neurotoxicity. Accordingly, this study was designed to investigate the possible protective activity of aqueous Phyllanthus amarus leaf extract (APALE) in HgCl2-exposed rats using standard neurobehavioral assessments. Thirty adult Wistar rats were randomized into six groups of five rats each viz: A: Control, distilled water; B: HgCl2 (4 mg/kg body wt.); C: APALE (200 mg/kg body wt.) + HgCl2 (4 mg/kg); D: APALE (400 mg/kg body wt.) + HgCl2 (4 mg/kg); E: APALE (200 mg/kg body wt.); F: APALE (400 mg/kg body wt.). All administrations were through an orogastric tube for 14 days. Thereafter, neurobehavioral tests (open field, novel object and Y-maze) were done and experimental rats were sacrificed by cervical dislocation. Body, brain and cerebellar weights were examined across all groups. HgCl2 exposure significantly (p<0.0.05) decreased whole body weight across experimental groups. Similarly, a reduction in brain and cerebellar weight was observed. Significant neurobehavioral alterations to locomotion, discrimination index and cognition/memory, induced by HgCl2, were observed across experimental groups. However, protection against the deleterious effects induced by HgCl2 was observed following pretreatment with APALE. Conclusively, these findings show that APALE demonstrated potent protective activity against HgCl2-induced neurotoxicity and may be useful in the management of Hg toxicity and other related disorders. [ABSTRACT FROM AUTHOR]

Mercury (Hg) exposure is known to damage vital components of the central nervous system primarily through oxidative stress. Although Phyllanthus amarus (PA) is reported to be rich in antioxidants, there is a dearth of relevant research evidence to show its protective activity against Mercuric chloride (HgCl2)-induced neurotoxicity. Accordingly, this study was designed to investigate the possible protective activity of aqueous Phyllanthus amarus leaf extract (APALE) in HgCl2-exposed rats using standard neurobehavioral assessments. Thirty adult Wistar rats were randomized into six groups of five rats each viz: A: Control, distilled water; B: HgCl2 (4 mg/kg body wt.); C: APALE (200 mg/kg body wt.) + HgCl2 (4 mg/kg); D: APALE (400 mg/kg body wt.) + HgCl2 (4 mg/kg); E: APALE (200 mg/kg body wt.); F: APALE (400 mg/kg body wt.). All administrations were through an orogastric tube for 14 days. Thereafter, neurobehavioral tests (open field, novel object and Y-maze) were done and experimental rats were sacrificed by cervical dislocation. Body, brain and cerebellar weights were examined across all groups. HgCl2 exposure significantly (p

Consumption of a high-fat diet has adverse impacts on metabolism, neurobehavioral, and neurochemical homeostasis in both humans and experimental animals. Here, we examined the effects of two different cultivars of Corylus avellana L. in a mouse model of metabolic syndrome. Corylus avellana L. reduced weight gain in mice that were treated with a high-fat diet, improved their behavioral parameters as exemplified by locomotion and rearing, working-memory, and reduced grooming and anxiety indices. Both Corylus avellana L. varieties reduced blood glucose levels and lipid peroxidation, improved lipid profile, and antioxidant status in mice placed on a high fat diet. Finally, brain acetylcholinesterase activity was also reduced, dopamine level was increased, while caspase-3 level was reduced. Thus, the Corylus avellana L. cultivars improve metabolic, behavioral, and neurochemical homeostasis in a diet with a high-fat content.

Background: This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). Methods: In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. Findings: Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. Interpretation: FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. Funding: This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

Abstract Background Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption. Methods The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline. Discussion The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.

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In this study, the persistent effects of embryonic exposure to fenbuconazole (FBZ), a triazole fungicide, on neurobehaviour in zebrafish were investigated. After exposure of fertilized eggs to FBZ for 72 h (h), the larvae were cultured to adulthood in clean water. In adult zebrafish embryonically exposed to 50 and 500 ng L−1 FBZ, the ratio of brain weight/body weight was significantly decreased, and the number of apoptotic cells in the brain was significantly increased, accompanied by upregulated protein levels of P53 and downregulated levels of BCL2. The novel tank test showed a significant reduction in the moved distance and speed, and a longer period of adaptation to new environments in the 500 ng L−1 group. The social preference experiment showed impaired social interaction behaviour and reduced time of aggregation in the 500 ng L−1 group. Increased dopamine and norepinephrine levels in the brain might be responsible for this anxiety-like behaviour. In addition to upregulated protein levels of tyrosine hydroxylase and β 2 -adrenoceptor, the transcription of genes related to dopamine and norepinephrine synthesis in the brain such as th1 , th2 , ddc , drd1b , dat , and dbh, was increased. The methylation levels of related genes were reduced, which were matched with their increased transcriptional levels. These results demonstrate that embryonic FBZ exposure might cause persistent neurotoxicity in adulthood, which suggests the rational cautious use of FBZ. [Display omitted] • Embryonic exposure to FBZ caused impairments on neurobehavior in adult zebrafish. • FBZ reduced the brain/body index and increased number of apoptotic cells in the adult brain. • The synthesis of dopamine (DA) and norepinephrine (NE) in the adult brain was enhanced. • Reduced methylation levels of related genes matched with their increased transcription. [ABSTRACT FROM AUTHOR]

The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory.

Cyclophosphamide use has been associated with increased oxidative stress in cells and tissues. Quercetin's antioxidative properties make it of potential benefit in such conditions of oxidative stress. To assess quercetin's ability to mitigate cyclophosphamide–induced organ toxicities in rats. Sixty rats were assigned into six groups. Groups A and D served as normal and cyclophosphamide control and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin at 200 mg/kg of feed. Groups A-C received intraperitoneal (ip) normal saline on days 1 and 2, while D-F received ip cyclophosphamide (150 mg/kg/day on days 1 and 2). On day 21, behavioural tests were carried out, animals were sacrificed and blood samples taken. Organs were processed for histological study. Quercetin reversed cyclophosphamide-induced decrease in body weight, food intake and total antioxidant capacity, and increase in lipid peroxidation (p = 0.001), It also reversed derangement in levels of liver transaminase, urea, creatinine and proinflammatory cytokines (p = 0.001). Improvement in working-memory and anxiety-related behaviours were also observed. Finally, quercetin reversed alterations in levels of acetylcholine, dopamine and brain-derived neurotropic factor (p = 0.021); while reducing serotonin levels and astrocyte immunoreactivity. Quercetin shows significant ability to protect against cyclophosphamide-induced changes in rats. [ABSTRACT FROM AUTHOR]

Cerebellar haemorrhage accounts for 5–10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models. [ABSTRACT FROM AUTHOR]

Nicotine is a neuro-stimulant that has been implicated in the pathophysiology of many brain diseases. The need to prevent or alleviate the resulting dysfunction is therefore paramount, which has also given way to the use of medicinal plants in the management of brain conditions. This study was designed to determine the histomorphological and neurobehavioural changes in the cerebellum of Wistar rats following nicotine insult and how such injuries respond to Moringa intervention. Twenty-four adult male Wistar rats were divided into 4 groups. Group A and B were orally treated with normal saline and Moringa oleifera respectively for twenty-eight days; Group C was treated with nicotine while group D was treated orally with Moringa oleifera and intraperitoneally with nicotine for twenty-eight days. Animals were subjected to the open field test on the last day of treatment. 24 h after last day treatment, the animals were anesthetized and perfusion fixation was carried out. The cerebellum was excised and post-fixed in 4% paraformaldehyde and thereafter put through routine histological procedures. Results revealed cytoarchitectural distortion and extreme chromatolysis in neuronal cells of the cerebellar cortical layers in the nicotine-treated group. The Purkinje cells of the cerebellum of animals in this group were degenerated. There were also reduced locomotor activities in the group. Moringa was able to prevent the chromatolysis, distortion of the cerebellar cortical cells and neurobehavioural deficit. Our result suggests that Moringa oleifera could prevent nicotine-induced cerebellar injury in Wistar rats, with the possibility of ameliorating the clinical features presented in associated cerebellar pathology. [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate the abnormalities in the development of rat brains, livers, kidney and behaviours after drinking desalinated seawater prenatally. Three types of drinking water were employed as an experimental probe (bottled water, filtered desalinated seawater and tap desalinated seawater) to investigate neurobehavioral and morphological changes in the development of pup rats. Female rats from each group were administered water from their birth until gestation and lactation. The 1st and 2nd generation pups were divided into three groups: Group C, mothers and pups administered with bottled drinking water (the control group); Group F, mothers and pups administered with filtered drinking water; Group T, mothers and pups administered with unfiltered desalinated seawater (tap water). Morphological changes (CNS aberration) and neurobehavioral changes were studied. The aberrations recorded in the tissues (brain, liver, kidney and spinal cord) of rats from groups T and F may be due to oxidative stress in these tissues such as reduced glutathione, lipid peroxidation, peroxidase and super oxide dismutase. In conclusion, drinking desalinated seawater for a long time may cause teratogenic effects in the development of New-born rats. [ABSTRACT FROM AUTHOR]

Objective We assessed the impacts of silymarin co-administration on aspartame-induced changes in novelty-induced behaviours, memory, anxiety-related behaviours, cerebral antioxidant status and histomorphology in mice. Method Six groups of mice were administered vehicle (distilled water), silymarin (25 mg/kg), aspartame (at 160 or 320 mg/kg), and silymarin (25 mg/kg) co-administered with aspartame at 160 or 320 mg/kg daily for 21 days, via an oral cannula. Behaviours were assessed after the first and last dose of treatment. Animals were sacrificed thereafter. Brain homogenates were used to assess antioxidant status; while sections of the cerebral cortex were processed for routine histology. Result Repeated co-administration of silymarin with aspartame resulted in significant suppression of horizontal locomotion and rearing, while grooming behaviour was enhanced; when compared to aspartame alone. Spatial working-memory showed significant improvement only after acute co-administration, while anxiety-related behaviours were reduced after repeated administration of both silymarin and aspartame. Cerebral cortical morphological integrity was better preserved, and astrocytic reactivity reduced with silymarin co-administration. Brain activity of superoxide dismutase and nitric oxide levels were decreased, while glutathione peroxidase activity was increased, when compared to levels seen with aspartame alone. Conclusion The study shows that co-administration of silymarin with aspartame was associated with significant attenuation of central effects, when compared to administration of aspartame alone. [ABSTRACT FROM AUTHOR]

Maternal weight before and during pregnancy is associated with offspring neurobehaviour in childhood. We investigated maternal weight prior to and during pregnancy in relation to neonatal neurobehaviour. We hypothesized that maternal obesity and excessive gestational weight gain would be associated with poor neonatal attention and affective functioning. Participants ( n = 261) were recruited, weighed and interviewed during their third trimester of pregnancy. Pre-pregnancy weight was self-reported and validated for 210 participants, with robust agreement with medical chart review ( r = 0.99). Neurobehaviour was measured with the NICU Network Neurobehavioural Scale (NNNS) administered on Days 2 and 32 postpartum. Maternal exclusion criteria included severe or persistent physical or mental health conditions (e.g. chronic disease or diagnoses of Bipolar Disorder or Psychotic Spectrum Disorders), excessive substance use, and social service/foster care involvement or difficulty understanding English. Infants were from singleton, full-term (37-42 weeks gestation) births with no major medical concerns. Outcome variables were summary scores on the NNNS ( n = 75-86). For women obese prior to pregnancy, those gaining in excess of Institute of Medicine guidelines had infants with poorer regulation, lower arousal and higher lethargy. There were no main effects of maternal pre-pregnancy body mass index on neurobehaviour. Women gaining above Institute of Medicine recommendations had neonates with better quality of movement. Additional studies to replicate and extend results past the neonatal period are needed. Results could support underlying mechanisms explaining associations between maternal perinatal weight and offspring outcomes. These mechanisms may inform future prevention/intervention strategies. © 2016 Blackwell Publishing Ltd [ABSTRACT FROM AUTHOR]

Intake of herbs and some of their constituents is reported to reduce risks of some diseases, with Allium sativum being one of such. This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. Twenty-four male Wistar rats were divided into 4 groups (n = 6). Group 1 was the control and received distilled water placebo orally, while groups 2-4 received oral doses of 78 mg/kg, 156 mg/kg and 312 mg/kg Allium sativum extract for 28 days. On day 29, spontaneous alternation behavioural test was carried out, and immediately the rats were anaesthetized (50 mg/kg ketamine hydrochloride IP.) and perfusion-fixed with 10% buffered formalin. The whole brains were removed and the medial prefrontal cortex excised and processed for histomorphologic studies by haematoxylin and eosin, and cresyl fast violet techniques. Neurobehavioural test revealed less spontaneous alternation in 156 mg/kg Allium sativum group, while the prefrontal cortices of the test groups showed hypertrophy, hyperplasia, pyknosis, karyorrhexis, chromatolysis, loss of brain cellular membranes and Nissl substance. The 156 mg/kg Allium sativum group showed altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type IIIA (MPS IIIA) is an inherited metabolic disorder caused by a lysosomal enzyme deficiency resulting in heparan sulphate (HS) accumulation and manifests with a progressive neurodegenerative phenotype. A naturally occurring MPS IIIA mouse model is invaluable for preclinical evaluation of potential treatments but the ability to effectively assess neurological function has proved challenging. Here, the aim was to evaluate a set of behaviour tests for their reliability in assessing disease progression in the MPS IIIA mouse model. Compared to wild-type (WT) mice, MPS IIIA mice displayed memory and learning deficits in the water crossmaze from mid-stage disease and locomotor impairment in the hind-limb gait assessment at late-stage disease, supporting previous findings. Declined wellbeing was also observed in the MPS IIIA mice via burrowing and nest building evaluation at late-stage disease compared to WT mice, mirroring the progressive nature of neurological disease. Excessive HS accumulation observed in the MPS IIIA mouse brain from 1 month of age did not appear to manifest as abnormal behaviours until at least 6 months of age suggesting there may be a threshold of HS accumulation before measurable neurocognitive decline. Results obtained from the open field and three-chamber sociability test are inconsistent with previous studies and do not reflect MPS IIIA patient disease progression, suggesting these assessments are not reliable. In conclusion, water cross-maze, hind-limb gait, nest building and burrowing, are promising assessments in the MPS IIIA mouse model, which produce consistent results that mimic the human disease., Competing Interests: None., (© 2023 The Authors.)

Background: More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age.Methods/design: This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay).Discussion: Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes.Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013. [ABSTRACT FROM AUTHOR]

Background Infants born <30 weeks' gestation are at increased risk of long term neurodevelopmental problems compared with term born peers. The predictive value of neurobehavioural examinations at term equivalent age in very preterm infants has been reported for subsequent impairment. Yet there is little knowledge surrounding earlier neurobehavioural development in preterm infants prior to term equivalent age, and how it relates to perinatal factors, cerebral structure, and later developmental outcomes. In addition, maternal psychological wellbeing has been associated with child development. Given the high rate of psychological distress reported by parents of preterm children, it is vital we understand maternal and paternal wellbeing in the early weeks and months after preterm birth and how this influences the parent-child relationship and children's outcomes. Therefore this study has aims to examine how 1) early neurobehaviour and 2) parental mental health relate to developmental outcomes for infants born preterm compared with infants born at term. Methods/Design This prospective cohort study will describe the neurobehaviour of 150 infants born at <30 weeks' gestational age from birth to term equivalent age, and explore how early neurobehavioural deficits relate to brain growth or injury determined by magnetic resonance imaging, perinatal factors, parental mental health and later developmental outcomes measured using standardised assessment tools at term, one and two years' corrected age. A control group of 150 healthy term-born infants will also be recruited for comparison of outcomes. To examine the effects of parental mental health on developmental outcomes, both parents of preterm and term-born infants will complete standardised questionnaires related to symptoms of anxiety, depression and post-traumatic stress at regular intervals from the first week of their child's birth until their child's second birthday. The parent-child relationship will be assessed at one and two years' corrected age. Discussion Detailing the trajectory of infant neurobehaviour and parental psychological distress following very preterm birth is important not only to identify infants most at risk, further understand the parental experience and highlight potential times for intervention for the infant and/or parent, but also to gain insight into the effect this has on parent-child interaction and child development. [ABSTRACT FROM AUTHOR]

Plasticity is an intrinsic property of the central nervous system, reflecting its capacity to respond in a dynamic manner to the environment and experience via modification of neural circuitry. In the context of healthy development, plasticity is considered beneficial, facilitating adaptive change in response to environmental stimuli and enrichment, with research documenting establishment of new neural connections and modification to the mapping between neural activity and behaviour. Less is known about the impact of this plasticity in the context of the young, injured brain. This review seeks to explore plasticity processes in the context of early brain insult, taking into account historical perspectives and building on recent advances in knowledge regarding ongoing development and recovery following early brain insult, with a major emphasis on neurobehavioural domains. We were particularly interested to explore the way in which plasticity processes respond to early brain insult, the implications for functional recovery and how this literature contributes to the debate between localization of brain function and neural network models. To this end we have provided an overview of normal brain development, followed by a description of the biological mechanisms associated with the most common childhood brain insults, in order to explore an evidence base for considering the competing theoretical perspectives of early plasticity and early vulnerability. We then detail these theories and the way in which they contribute to our understanding of the consequences of early brain insult. Finally, we examine evidence that considers key factors (e.g. insult severity, age at insult, environment) that may act, either independently or synergistically, to influence recovery processes and ultimate outcome. We conclude that neither plasticity nor vulnerability theories are able to explain the range of functional outcomes from early brain insult. Rather, they represent extremes along a ‘recovery continuum’. Where a child’s outcome falls along this continuum depends on injury factors (severity, nature, age) and environmental influences (family, sociodemographic factors, interventions). [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Unwanted effects of drugs on neurobehavioural and cardiovascular functions are normally assessed in separate studies and using different animals. A new model using dogs which allows for the integration of these assessments into a single study was established and validated, adopting the most sophisticated technologies for both monitoring behaviour by video recordings and cardiovascular parameters by telemetry. Methods: Conscious male beagle dogs (n =4) were given single oral doses of vehicle, and d-amphetamine (0.25, 0.75, 1.5 mg/kg) or acepromazine (0.05, 0.3, 2 mg/kg) within two different studies. Blood pressure, heart rate, electrocardiogram (EKG), body temperature, motor activity and behaviour (by video) were monitored continuously for 24 h post-dose. Animals underwent a full neurobehavioural examination the day before dosing, at the time to the maximal plasma concentration (Tmax) and 24 h post-dose. Results: d-Amphetamine: a dose-dependent increase in arterial blood pressure was noted at all doses and was generally associated with an increase in the QA interval, an index of cardiac contractility. Heart rate also increased but only at the 1.5 mg/kg dose. A dose-dependent general excitatory state of the nervous system was observed, characterised mainly by hyper-reactivity, and stereotyped activities. Acepromazine: a decrease in systolic blood pressure was detected at 0.3 and 2 mg/kg generally associated with a decrease in pulse pressure reflecting a negative inotropic effect. A dose-related increase in heart rate accompanied this effect. Dose-dependent general depression of the nervous system was noted; mainly characterised by half-closed eyes, subdued behaviour and impaired posture. In both studies, all dogs completely recovered at approximately 16 h after treatment. Discussion: Cardiovascular and neurobehavioural changes expected from the pharmacology of test substances were accurately detected. No significant fluctuations of the telemetric parameters recorded were noted as a consequence of the handling associated with the direct neurobehavioural examination. These results confirm the validity of this combined model capable of providing a reliable neurobehavioural and cardiovascular assessment of drugs. [Copyright &y& Elsevier]

Abstract: The health risks of inhalation exposure to volatile organic solvents may not only depend on the total external dose, but also on the pattern of exposure. It has been suggested that exposure to regularly occurring peak concentrations may have a stronger impact on the brain than constant exposure at the same average level. Recent animal experimental studies conducted in our laboratory using relatively high concentrations of toluene have shown different effects on discrimination performance and motor activity during and after exposure, depending on the exposure scenario. Relevance of these findings for man was evaluated in a volunteer study in which 11 healthy men (age 20–49 years) were exposed by inhalation for 4h to either a constant concentration of 40ppm toluene or to three 30-min exposure peaks at 110ppm during this 4h period. Selected tests from the Neurobehavioural Evaluation System (NES) were performed repeatedly during and after exposure. Blood concentrations of toluene as well as urinary o-cresol excretion were measured at relevant time points. The results show that toluene concentration in blood increased during constant exposure and fluctuated during occupationally relevant peak exposures. Presumably, brain concentrations showed similar qualitative patterns. No clear changes were observed on neurobehavioural measures of motor performance, attention, perceptual coding and memory, or on measures of mood and affect. The exposure conditions do not seem to induce significant acute changes in central nervous system function similar to those observed at much higher concentrations in animals, although a statistical correlation was found between one motor performance test (Finger Tapping Test with alternating hands) and blood toluene concentrations. Urinary o-cresol excretion appeared to be significantly higher during the first 2h after exposure. [Copyright &y& Elsevier]

Gliclazide (GLD), a sulphonylurea is efficacious in the treatment of diabetes type-2. However, there is limited information on its activity in the brain, especially in diabetics. This research investigated the brain activities of GLD following streptozotocin-induced diabetes in Wistar rats. Twenty five adult male Wistar rats (200-250 g) were grouped (n = 5) as: Control (distilled water, 5 mL/kg) and GLD (150 mg/kg) groups; and the diabetic groups, untreated streptozotocin (STZ, 35 mg/kg), and STZ (35 mg/kg) treated with GLD (150 mg/kg) for two and four weeks, and already on high fat diet. The animals' body weights and blood glucose levels were checked weekly. After the experimental duration, spontaneous alternation and novel object recognition tests were carried out and the animals sacrificed. Perfusion with phosphate buffered saline preceded brain excision for biochemical analyses, with halves fixed in 10% neutral buffered formalin for histology. Compared with the control, results showed (p < 0.05) declined spontaneous alternation and exploratory activities with no preference for familiar or novel objects, body weights loss, raised blood glucose, increased malondialdehyde with decreased superoxide dismutase concentrations, and no apparent adverse effect on hippocampal and prefrontal cortical Nissl substance in the untreated diabetic group. The adverse observations were attenuated in the GLD treated diabetic groups; although the spontaneous alternation in the four weeks GLD treated diabetic group improved (p < 0.05), exploration of objects increased (p < 0.05) without preference. The present results showed that treatment with GLD for two and four weeks mitigated STZ activities, even though there was less improvement in neurocognitive activities., (© 2022 The Authors.)

Introduction:  Prematurity (birth before 37 +0 weeks' gestation) is associated with wide-ranging neurodevelopmental impairment. Prognosis among moderate to late (32 +0 to <37 +0   weeks' gestation) preterm infants (MLPT) is better compared to their counterparts born very preterm (<32 +0  weeks' gestation). However the risk of developmental impairment among MLPT, who make up about 84% of all preterm infants, is 2-3 times higher when compared to infants born at term. Early interventions have aimed to improve outcomes in preterm infants generally, but there are limited data on their need and effect in MLPT specifically. Prioritising research, long-term follow-up and early interventions targeted at ameliorating the impact of preterm birth among MLPT is required. Objectives:  To conduct a systematic review of the type of early childhood interventions (from birth until 4 years of age) offered to  MLPT children and to evaluate their impact on neurodevelopmental outcomes (cognitive, neurobehavioural and motor) as assessed in these children during childhood (until 18 years of age). Methods and analysis:  A systematic literature search in Web of Science, Medline Ovid, PsycINFO, CINAHL and EMBASE will be conducted. Data on MLPT children receiving developmental interventions until the age of 4 years will be evaluated. Interventions may involve parents or primary caregivers. Primary outcomes are cognitive, neurobehavioural and motor development as measured from birth until the age of 18 years. The Cochrane Risk of Bias Assessment Tool will be used to evaluate the methodological quality of randomised controlled trials (RCTs) included in the review and will be graded as low, high  or unclear risk of bias. The quality of non-RCTs will be evaluated with the Newcastle-Ottawa Scale. The quality of evidence for each outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation Approach. Publication and reporting bias will be assessed using Egger's test and funnel plots respectively., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Agyeman-Duah J et al.)

Background: This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS)., Methods: In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted., Findings: Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty., Interpretation: FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers., Funding: This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.)., Competing Interests: Declaration of Competing Interests The authors have no conflict of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)