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Sleep is an essential component of development. Developmental sleep disruption (DSD) impacts brain maturation and has been associated with significant consequences on socio-emotional development. In humans, poor sleep during infancy and adolescence affects neurodevelopmental outcomes and may be a risk factor for the development of autism spectrum disorder (ASD) or other neuropsychiatric illness. Given the wide-reaching and enduring consequences of DSD, identifying underlying mechanisms is critical to best inform interventions with translational capacity. In rodents, studies have identified some mechanisms and neural circuits by which DSD causes later social, emotional, sensorimotor, and cognitive changes. However, these studies spanned methodological differences, including different developmental timepoints for both sleep disruption and testing, different DSD paradigms, and even different rodent species. In this scoping review on DSD in rodents, we synthesize these various studies into a cohesive framework to identify common neural mechanisms underlying DSD-induced dysfunction in brain and behavior. Ultimately, this review serves the goal to inform the generation of novel translational interventions for human developmental disorders featuring sleep disruption.

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Psychiatric disorders including major depression are twice as prevalent in women compared to men. This sex difference in prevalence only emerges after the onset of puberty, suggesting that puberty may be a sensitive period during which sex-associated vulnerability to stress-related depression might become established. Thus, this study investigated whether stress occurring specifically during the pubertal window of adolescence may be responsible for this sex difference in depression vulnerability. Male and female rats were exposed to a three-day stress protocol during puberty (postnatal days 35-37 in females, 45-47 in males) and underwent behavioral tests in adolescence or adulthood measuring anhedonia, anxiety-like behavior, locomotor activity and antidepressant-like behavior. Brainstem and striatum tissue were collected from a separate cohort of behavioral test-naïve rats in adolescence or adulthood to quantify the effect of pubertal stress on monoamine neurotransmitters. Pubertal stress increased immobility behavior in the forced swim test in both sexes in adolescence and adulthood. In adolescence, pubertal stress altered escape-oriented behaviors in a sex-specific manner: decreasing climbing in males but not females and decreasing swimming in females but not males. Pubertal stress decreased adolescent brainstem noradrenaline specifically in females and had opposing effects in adolescent males and females on brainstem serotonin turnover. Pubertal stress induced anhedonia in the saccharin preference test in adult males but not females, an effect paralleled by a male-specific decrease in striatal dopamine turnover. Pubertal stress did not significantly impact anxiety-like behavior or locomotor activity in any sex at either age. Taken together, these data suggest that although pubertal stress did not preferentially increase female vulnerability to depressive-like behaviors compared to males, stress during puberty exerts sex-specific effects on depressive-like behavior and anhedonia, possibly through discrete neurotransmitter systems.

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PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins (Semas), a large family of axonal guidance cues vital during neural development. PlxnA1 is expressed in embryonic interneurons, and PlxnA1 deletion in mice leads to less interneurons in the developing cortex. In addition, PlxnA1 has been identified as a schizophrenia susceptibility gene. In our previous study, PlxnA1 knockout (KO) mice under a BALB/cAJ genetic background exhibited significantly increased self-grooming and reduced prepulse inhibition, a reliable phenotype for investigating the neurobiology of schizophrenia. However, the mechanism underlying the abnormal behavior of PlxnA1 KO mice remains unclear. We first confirmed PlxnA1 mRNA expression in parvalbumin-expressing interneurons (PV cells) in the medial prefrontal cortex (mPFC) of adult mice. Immunohistochemical analysis (IHC) showed significantly decreased densities of both GABAergic neurons and PV cells in the mPFC of PlxnA1 KO mice compared with wild type mice (WT). PV cells were found to express molecule interacting with CasL 1 (MICAL1), an effector involved in Sema-Plxn signaling for axon guidance, suggesting MICAL1 and PlxnA1 co-expression in PV cells. Furthermore, IHC analysis of 8-oxo-dG, an oxidative stress marker, revealed significantly increased oxidative stress in PlxnA1-deficient PV cells compared with WT. Thus, increased oxidative stress and decreased PV cell density in the mPFC may determine the onset of PlxnA1 KO mice's abnormal behavior. Accordingly, deficient PlxnA1-mediated signaling may increase oxidative stress in PV cells, thereby disrupting PV-cell networks in the mPFC and causing abnormal behavior related to neuropsychiatric diseases.

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BACKGROUND: Cochlear ablation is one of the most classic methods for the animal model establishment of hearing loss (HL), but the vast majority of rodents taken by cochlear ablation have been rats and adult mice so far. Given the importance of mice in HL studies, it is urgently necessary to expand the application of cochlear ablation in mice at different ages. NEW METHOD: Bilateral cochlear ablation surgery was performed in C57BL/6 J mice before the onset of hearing at postnatal (P) day 10. Auditory brainstem response was performed to evaluate the hearing of mice. Open field test and swimming test were performed to examine the vestibular function of mice. RESULTS: A permanent HL model was built by bilateral cochlear ablation in C57BL/6 J mice at P10. This method could successfully destroy cochlear hair cells and cause no vestibular deterioration in the adulthood of mice. COMPARISON WITH EXISTING METHOD(S): In addition to transgenic mice, permanently deaf mice used in this field in the existing studies are restricted to a time point after their ear canal opening. This study is the first to establish a congenital and permanent HL mouse model by cochlear ablation without gene modification. CONCLUSIONS: Bilateral cochlear ablation in mice at P10 is an ideal and effective way for congenital HL mice model foundation, and the vestibular function seems not to be deteriorated.

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BACKGROUND: Efficient reproductive function is an important characteristic that has evolved through natural selection. Nutrition can modulate reproductive activities at different levels, and its effect on reproduction is deemed complex and less predictable. OBJECTIVE: This study aims at investigating the underlying effect of persistent dietary protein deficiency during early life on reproductive parameters of subsequent (F1 and F2) generations. METHOD: Rats in group of four (4) were fed daily, different ration of protein diet (PD) formulated as: 21% protein diet, 10%protein diet, 5%protein diet and control diet (rat chow, containing 16-18% protein). They were fed ad libitum before mating, throughout gestation and lactation, and next generations were weaned to the maternal diet. Reproductive function analysis (which include; gestation and pubertal hormonal profiling, onset of puberty, oestrus cyclicity, sexual response) and morphometric analysis of the ovarian structure were carried out to assess associated consequences. RESULTS: There was significant reduction in the fertility index (Control; 85.8%., 21%PD; 88.43%., as compared to 10%PD; 65.9%., 5%PD; 35.78%.,) at F1, also recurring in F2 respectively as a consequence of altered reproductive function in the protein deficient models at P ≤ 0.05. Low protein diet posed suboptimal intrauterine condition, which was linked to increased prenatal morbidity and mortality (control; 11.3%., 21%PD; 3.3%., 10%PD; 27.4%., 5%PD; 32.9%), low birthweight (control; 5.29, 4.9 g., 21%PD; 5.5, 5.06 g., 10%PD; 4.05, 3.86 g., 5%PD; 2.7, 2.5 g) at F1 and F2 respectively, delayed onset of puberty (with average pubertal age set at: control; PND 36, 21%PD; PND 38 while 10%PD; PND 62., and 5%PD; PND 67), followed by induced cycle irregularity, altered follicular maturation and endocrine dysfunction, more severe in 5%PD. CONCLUSION: Reproductive status of a female organism depends on the maintenance of ovarian structure and function that has been associated with the hypothalamic pituitary-gonadal axis, hormonal events and sexual maturity. There is therefore an association between persistent early life protein deficiency and reproductive response which mechanistically involves life-long changes in key ovarian cytoarchitecture and function.

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Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.

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INTRODUCTION: Several drugs of abuse (DOA) are capable of modulating neurohypophysial hormones, such as oxytocin (OT) and vasopressin (VP), potentially resulting in the development of psychological abnormalities, such as cognitive dysfunction, psychoses, and affective disorders. Efavirenz (EFV), widely used in Africa and globally to treat HIV, induces diverse neuropsychiatric side effects while its abuse has become a global concern. The actions of EFV may involve neurohypophysial system (NS) disruption like that of known DOA. This study investigated whether sub-chronic EFV exposure, at a previously-determined rewarding dose, alters peripheral OT and VP levels versus that of a control, ∆9-tetrahydrocannabinol (∆9-THC), methamphetamine (MA) and cocaine. MATERIALS AND METHODS: To simulate the conditions under which reward-driven behavior had previously been established for EFV, male Sprague Dawley rats (n = 16/exposure) received intraperitoneal vehicle (control) or drug administration across an alternating sixteen-day dosing protocol. Control administration (saline/olive oil; 0.2 ml) occurred on odd-numbered and drug administration (EFV: 5 mg/kg, ∆9-THC: 0.75 mg/kg, MA: 1 mg/kg, or cocaine: 20 mg/kg) on even-numbered days followed by euthanasia, trunk blood collection and plasma extraction for neuropeptide assay. Effect of drug exposure on peripheral OT and VP levels was assessed versus controls and quantified using specific ELISA kits. Statistical significance was determined by Kruskal-Wallis ANOVA, with p < 0.05. Ethics approval: NWU-00291-17-A5. RESULTS: Delta-9-THC reduced OT and VP plasma levels (p < 0.0001, p = 0.0141; respectively), cocaine reduced plasma OT (p = 0.0023), while MA reduced plasma VP levels (p = 0.0001), all versus control. EFV reduced OT and VP plasma levels (p < 0.0001; OT and VP) versus control, and similar to ∆9-THC. CONCLUSION: EFV markedly affects the NS in significantly reducing both plasma OT and VP equivalent to DOA. Importantly, EFV has distinct effects on peripheral OT and VP levels when assessed within the context of drug dependence. The data highlights a possible new mechanism underlying previously documented EFV-induced effects in rats, and whereby EFV may induce neuropsychiatric adverse effects clinically; also providing a deeper understanding of the suggested abuse-potential of EFV.

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Long-term cannabis use during adolescence has deleterious effects in brain that are largely ascribed to the activation of cannabinoid-1 receptors (CB1Rs) by delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive compound in marijuana. Systemic administration of ∆9-THC inhibits acetylcholine release in the prelimbic-prefrontal cortex (PL-PFC). In turn, PL-PFC acetylcholine plays a role in executive activities regulated by CB1R-targeting endocannabinoids, which are generated by cholinergic stimulation of muscarinic-1 receptors (M1Rs). However, the long-term effects of chronic administration of increasing doses of ∆9-THC in adolescent males on the distribution and function of M1 and/or CB1 receptors in the PL-PFC remains unresolved. We used C57BL\6J male mice pre-treated with vehicle or escalating daily doses of ∆9-THC to begin filling this gap. Electron microscopic immunolabeling showed M1R-immunogold particles on plasma membranes and in association with cytoplasmic membranes in varying sized dendrites and dendritic spines. These dendritic profiles received synaptic inputs from unlabeled, CB1R- and/or M1R-labeled axon terminals in the PL-PFC of both treatment groups. However, there was a size-dependent decrease in total (plasmalemmal and cytoplasmic) M1R gold particles in small dendrites within the PL-PFC of mice receiving ∆9-THC. Whole cell current-clamp recording in PL-PFC slice preparations further revealed that adolescent pretreatment with ∆9-THC attenuates the hyperpolarization and increases the firing rate produced by local muscarinic stimulation. Repeated administration of ∆9-THC during adolescence also reduced spontaneous alternations in a Y-maze paradigm designed for measures of PFC-dependent memory function in adult mice. Our results provide new information implicating M1Rs in cortical dysfunctions resulting from adolescent abuse of marijuana.

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Early-life stress (ES) increases the risk for psychopathology and cognitive decline later in life. Because the neurobiological substrates affected by ES (i.e., cognition, neuroplasticity, and neuroinflammation) are also altered in aging, we set out to investigate if and how ES in the first week of life affects these domains at an advanced age, and how ES modulates the aging trajectory per se. We subjected C57BL/6j mice to an established ES mouse model from postnatal days 2-9. Mice underwent behavioral testing at 19 months of age and were sacrificed at 20 months to investigate their physiology, hippocampal neuroplasticity, neuroinflammation, and telomere length. ES mice, as a group, did not perform differently from controls in the open field or Morris water maze (MWM). Hippocampal neurogenesis and synaptic marker gene expression were not different in ES mice at this age. While we find aging-associated alterations to neuroinflammatory gene expression and telomere length, these were unaffected by ES. When integrating the current data with those from our previously reported 4- and 10-month-old cohorts, we conclude that ES leads to a 'premature' shift in the aging trajectory, consisting of early changes that do not further worsen at the advanced age of 20 months. This could be explained e.g. by a 'floor' effect in ES-induced impairments, and/or age-induced impairments in control mice. Future studies should help understand how exactly ES affects the overall aging trajectory.

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This study is evaluating the effects of ethanol and nicotine exposure during pregnancy and lactation on placenta histology and follicular atresia in the first-generation (f1) mice pups. The experimental groups were 5 groups of NMRI pregnant mice, including: control, vehicle (received normal saline) ethanol (3 g/kg/day, 20 % v/v intraperitoneally), nicotine (1 mg/kg/day, subcutaneously), and ethanol plus nicotine which received both. Pregnant animals in each group were then divided into two groups, one group for examining the placenta that was treated for 18 days and the other group for the ovary of one-day-old (PND1) and fifty-six-day-old (PND56) female offspring who were treated for 42 days (during intrauterine development and lactation). After the autopsy procedure, histopathological and morphometrical observations were done. Data revealed that the exposed mice had a significant change in the placenta morphometry and histology as well as a marked increase in the number of ovarian TUNEL positive cells on postnatal days 1 and 56. Therefore, maternal exposure to alcohol and nicotine during developmental and lactation periods could lead to changes in the placenta properties as well as an increase in the apoptotic ovarian follicles in f1 mice pups.

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Early in the postnatal period, motoneuron axon stimulation can excite motor networks in the spinal cord. Here we tested if these excitatory effects changed across early postnatal development up to postnatal day (P) 24 by when mice are capable of weight-bearing locomotion and locomotor networks are considered functionally mature. This was accomplished in the isolated spinal cord preparation using ventral root evoked entrainment of disinhibited bursts. Ventral root evoked entrainment was defined and characterized over the first 2 weeks of postnatal development, and was found to decline over this period, but entrainment could still be detected in mice as old as P24. Disinhibited bursting could be elicited, and dorsal root evoked entrainment could be recorded as late as P39 and remained unchanged in effectiveness, suggesting that poor tissue viability may not be the cause of the decline in ventral root evoked entrainment. Pharmacological experiments performed on younger animals established that dopamine D2 receptor antagonists and mGluR1 agonists both enhanced ventral root evoked entrainment. In conclusion, the motoneuronal inputs to spinal motor networks via the excitatory pathway is modulated by dopamine and metabotropic glutamate receptors and may be under powerful inhibitory control, which may explain why there is a developmental decline in entrainment.

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Exposure to early-life stress (ELS) increases risk for poor mental and physical health outcomes that emerge at different stages across the lifespan. Yet, how age interacts with ELS to impact the expression of specific phenotypes remains largely unknown. An established limited-bedding paradigm was used to induce ELS in mouse pups over the early postnatal period. Initial analyses focused on the hippocampus, based on documented sensitivity to ELS in humans and various animal models, and the large body of data reporting anatomical and physiological outcomes in this structure using this ELS paradigm. An unbiased discovery proteomics approach revealed distinct adaptations in the non-nuclear hippocampal proteome in male versus female offspring at two distinct developmental stages: juvenile and adult. Gene ontology and KEGG pathway analyses revealed significant enrichment in proteins associated with mitochondria and the oxidative phosphorylation (OXPHOS) pathway in response to ELS in female hippocampus only. To determine whether the protein adaptations to ELS reflected altered function, mitochondrial respiration (driven through complexes II-IV) and complex I activity were measured in isolated hippocampal mitochondria using a Seahorse X96 Flux analyzer and immunocapture ELISA, respectively. ELS had no effect on basal respiration in either sex at either age. In contrast, ELS increased OXPHOS capacity in juvenile males and females, and reduced OXPHOS capacity in adult females but not adult males. A similar pattern of ELS-induced changes was observed for complex I activity. These data suggest that initial adaptations in juvenile hippocampus due to ELS were not sustained in adults. Mitochondrial adaptations to ELS were also exhibited peripherally by liver. Overall, the temporal distinctions in mitochondrial responses to ELS show that ELS-generated adaptations and outcomes are complex over the lifespan. This may contribute to differences in the timing of appearance of mental and physical disturbances, as well as potential sex differences that influence only select outcomes.

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Levomepromazine (LMP) is a phenothiazine neuroleptic drug with strong analgesic and sedative properties that is increasingly used off-label in pediatrics and is being discussed as an adjunct therapy in neonatal intensive care. Basic research points towards neuroprotective potential of phenothiazines, but LMP's effect on the developing brain is currently unknown. The aim of the present study was to assess LMP as a pharmacologic strategy in established neonatal in vitro and in vivo models of the healthy and injured developing mouse brain. In vitro, HT-22 cells kept exposure-naïve or injured by glutamate were pre-treated with vehicle or increasing doses of LMP and cell viability was determined. In vivo, LMP's effects were first assessed in 5-day-old healthy, uninjured CD-1 mouse pups receiving a single intraperitoneal injection of vehicle or different dosages of LMP. In a second step, mouse pups were subjected to excitotoxic brain injury and subsequently treated with vehicle or LMP. Endpoints included somatometric data as well as histological and immunohistochemical analyses. In vitro, cell viability in exposure-naïve cells was significantly reduced by high doses of LMP, but remained unaffected in glutamate-injured cells. In vivo, no specific toxic effects of LMP were observed neither in healthy mouse pups nor in experimental animals subjected to excitotoxic injury, but body weight gain was significantly lower following higher-dose LMP treatment. Also, LMP failed to produce a neuroprotective effect in the injured developing brain. Additional studies are required prior to a routine clinical use of LMP in neonatal intensive care units.

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The aim of study was to investigate the relationships among serum diamine oxidase (DAO) activity, postnatal days and the plasma copper (Cu) concentration, using calves with or without diarrhea. In healthy calves, the serum DAO activity was significantly higher at 2 postnatal days than at ≥7 postnatal days, and no significant changes were observed after 7 postnatal days. In addition, no significant correlation was found between serum DAO activity and plasma Cu concentration at all postnatal days in healthy calves. Although, the serum DAO activity in 14 diarrheic calves (66.78 ± 14.37 IU/ml) was lower than that in 19 healthy calves (170.33 ± 97.83 IU/ml, P<0.01), plasma Cu concentrations in all calves remained within the normal range.

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OBJECTIVE: The authors sought to determine if hydrocephalus caused a proinflammatory state within white matter as is seen in many other forms of neonatal brain injury. Common causes of hydrocephalus (such as trauma, infection, and hemorrhage) are inflammatory insults themselves and therefore confound understanding of how hydrocephalus itself affects neuroinflammation. Recently, a novel animal model of hydrocephalus due to a genetic mutation in the Ccdc39 gene has been developed in mice. In this model, ciliary dysfunction leads to early-onset ventriculomegaly, astrogliosis, and reduced myelination. Because this model of hydrocephalus is not caused by an antecedent proinflammatory insult, it was utilized to study the effect of hydrocephalus on inflammation within the white matter of the corpus callosum. METHODS: A Meso Scale Discovery assay was used to measure levels of proinflammatory cytokines in whole brain from animals with and without hydrocephalus. Immunohistochemistry was used to measure macrophage activation and NG2 expression within the white matter of the corpus callosum in animals with and without hydrocephalus. RESULTS: In this model of hydrocephalus, levels of cytokines throughout the brain revealed a more robust increase in classic proinflammatory cytokines (interleukin [IL]-1ß, CXCL1) than in immunomodulatory cytokines (IL-10). Increased numbers of macrophages were found within the corpus callosum. These macrophages were polarized toward a proinflammatory phenotype as assessed by higher levels of CD86, a marker of proinflammatory macrophages, compared to CD206, a marker for antiinflammatory macrophages. There was extensive structural damage to the corpus callosum of animals with hydrocephalus, and an increase in NG2-positive cells. CONCLUSIONS: Hydrocephalus without an antecedent proinflammatory insult induces inflammation and tissue injury in white matter. Future studies with this model will be useful to better understand the effects of hydrocephalus on neuroinflammation and progenitor cell development. Antiinflammatory therapy for diseases that cause hydrocephalus may be a powerful strategy to reduce tissue damage.

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Diabetes during pregnancy has been shown to affect the central nervous system (CNS) of the offspring, resulting in short- and long-term adverse effects. Children of diabetic mothers are more likely to develop cognitive impairment, also having increased susceptibility to psychiatric disorders. Microglia, the immune cells of the CNS, work as sensors of environmental changes, namely metabolic challenges, as early as the intrauterine period. During this period, microglia is actively involved in processes of neurogenesis, synaptic pruning and detection of any environmental alteration that may impact brain development. The remarkable sex dimorphism in neurodevelopment, as well as sex differences in the morphology and immune function of microglia during development, led us to clarify if maternal diabetes affects specific behavioral traits and microglia morphology during infancy in a sex-specific manner. Another important goal of this study was to clarify if insulin, the gold standard treatment of diabetes during gestation, could prevent maternal diabetes-induced behavioral changes, as well as microglia morphology, also considering sex specificities. Other molecular and cellular players potentially involved in the link between changes in metabolism and behavior were also analyzed in the hippocampus, a brain region implicated in cognition and other behavioral outcomes. Diabetes during pregnancy globally delayed female and male offspring development and was associated with impairments in recognition memory, but only in female offspring. In line with these results, at early and late infancy, some molecular and cellular markers were altered in offspring hippocampus in a sex-specific manner. The strict control of glycemia by insulin during pregnancy prevented most of the negative effects induced by uncontrolled hyperglycemia. Notably, insulin administration to diabetic dams may also modulate offspring development in a way that differs from what is observed in physiological conditions, since it promoted the expedited acquisition of developmental milestones and of discrimination ability at memory test, also inducing a hyper-ramification of male and female hippocampal microglia. Importantly, this study highlights the importance of analyzing the impact of maternal diabetes and insulin therapy, taking into account sex differences, since male and female present different vulnerabilities to hyperglycemia in this critical period of life.

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Brain oxidative signaling pathways have been identified as important targets for alleviating food deprivation-induced changes in metabolic gate-ways. Previous studies have shown that prenatal and early postnatal malnutrition alters leptin and ghrelin signaling via oxidative pathways. Thus, it has been hypothesized that agents with antioxidant properties might be beneficial for the mitigation of prenatal and early postnatal food scarcity-induced oxidative damage. Quercetin and kaempferol are natural bioflavonoids with proven antioxidant properties. In this study, we evaluated their effects on prenatal maternal food consumption, maternal and pup weights, biomarkers of orexigenic and anorexigenic hormones and oxidative stress in rats. Rats were allotted into different treatment groups (n â€‹= â€‹6) in three different experiments (prenatal, postnatal food-deprivations or both). Prenatal-food restriction (PrNFR) was induced by 50% of ad libitum accessible diet during pregnancy till parturition and postnatal-food restriction (PsNFR) was simulated by litter-enlargement to 16 pups per mother from postnatal day (PND) 2. Rats in each experiment were concurrently treated with vehicle (10 â€‹mL/kg), quercetin (50, 100 and 200 â€‹mg/kg, p.o.) or kaempferol (50, 100 and 200 â€‹mg/kg, p.o.) respectively. A third experimental group consisted of both protocols. Quercetin and kaempferol dose-dependently increased the body weights of pups exposed to PrNFR, PsNFR and PrNFR-PsNFR at PNDs 1-22 respectively. Both compounds increased maternal body weights but attenuated maternal food-intake at prenatal days 7 and 14 due by PrNFR. Quercetin and kaempferol reduced brain malondialdehyde concentrations and increased glutathione levels in PrNFR, PsNFR and PrNFR-PsNFR-exposed offspring of rats. Importantly, quercetin and kaempferol significantly (p â€‹< â€‹0.05) prevented PrNFR-, PsNFR- or PrNFR-PsNFR-induced alterations in leptin and ghrelin levels. Cumulatively, quercetin and kaempferol increased pup and maternal weights and attenuated maternal food-intake of rats submitted to PrNFR, PsNFR and PrNFR-PsNFR respectively, likely via nutrigenomic modulations of orexigenic/anorexigenic hormones and inhibition of brain oxidative stress.

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Some endocrine-disrupting chemicals (EDCs) can affect the endocrine system through covalent interactions with specific sites, leading to deregulation of physiological homeostasis. The acrylamide (AA) present in some fried or baked foods is an example of an electrophile molecule that is able to form adducts with nucleophilic regions of nervous system proteins leading to neurological defects. A positive correlation between increased urinary AA metabolite concentration and reduced levels of thyroid hormones (TH) was described in adolescents and young adults. Thus, this study aimed to evaluate whether AA affects the physiology of the hypothalamus-pituitary-thyroid (HPT) axis and the possible repercussions in peripheral TH-target systems. For this, male Wistar rats were exposed to doses of 2.5 or 5.0 mg AA/Kg/day, based on the LOAEL (Lowest Observed Adverse Effect Level) during prepubertal development. The expression of molecular markers of HPT functionality was investigated in the hypothalamus, pituitary, thyroid, heart and liver, as well as the hormonal and lipid profiles in blood samples. Herein, we showed that AA acts as EDCs for thyroid gland function, increasing the transcript expression of several proteins related to TH synthesis and altering hypothalamus-pituitary-thyroid axis homeostasis, an effect evidenced by the higher levels of THs in the serum. Compensatory mechanisms were observed in TH-target tissues, such as an increase in Dio3 mRNA expression in the liver and a reduction in Mct8 transcript content in the hearts of AA-treated rats. Together, these results pointed out an allostatic regulation of the HPT axis induced by AA and suggest that chronic exposure to it, mainly associated with food consumption, might be related to the higher prevalence of thyroid dysfunctions.

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Bilateral eye enucleation at birth (BE) leads to an expansion of the primary somatosensory cortex (S1) in rat pups. Although increased growth of the somatosensory thalamo-cortical afferents (STCAs) in part explains S1 expansion, timing mechanisms governing S1 formation are also involved. In this work, we begin the search of a developmental clock by intending to document the existence of putative clock neurons in the somatosensory thalamus (VPM) and S1 based upon changes of spontaneous spike amplitude; a biophysical property sensitive to circadian regulation; the latter known to be shifted by enucleation. In addition, we also evaluated whether STCAs growth rate and segregation timing were modified, as parameters the clock might time. We found that spontaneous spike amplitude transiently, but significantly, increased or decreased in VPM and S1 neurons of BE rat pups, respectively, as compared to their control counterparts. The growth rate and segregation timing of STCAs was, however, unaffected by BE. These results support the existence of a developmental clock that ticks differently in the VPM and S1 after BE. This observation, together with the fact that STCAs growth rate and segregation timing is unchanged, suggests that S1 expansion in BE rats may in part be controlled at the cortical level.

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In this research, we intended to evaluate the expression pattern, distribution and sources of Galectin-3 (Gal-3) in perinatal hypoxic-ischemic brain injury rat model. Postnatal day 3 Sprague-Dawley rat pups were subjected to right carotid artery ligation followed by 2.5 h of hypoxia (6% oxygen). Expression and distribution of Gal-3 were evaluated by western blotting and immunofluorescence. Sources of Gal-3 were evaluated by double staining with neuronic, oligodendrocytic, astrocytic, microglial and endotheliocytic markers. Our results indicated Gal-3 significantly upregulated from 12 h and maintained an increasing tendency within 72 h post injury. Although the relative expression of Gal-3 decreased after 72 h, we detected significant differences until 14d. We found Gal-3 started to distribute in cortex and thalamus area and maintained an increasing tendency. Gal-3 could be detected in cortex, thalamus, corpus callosum and hippocampus area at 72 h post injury. After that, expression of Gal-3 in cortex and thalamus area downregulated, the expression in corpus callosum and hippocampus area vanished. We found astrocyte, microglia, neuron and endotheliocyte were sources of Gal-3 in cortex area; astrocyte, microglia and endotheliocyte were sources of Gal-3 in thalamus area; oligodendrocyte precursor cell and endotheliocyte were sources of Gal-3 in corpus callosum; neuron, microglia and endotheliocyte were sources of Gal-3 in hippocampus. In conclusion, we demonstrated spatiotemporal expression patterns of Galectin-3 post perinatal hypoxic-ischemic brain injury in this research.

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