Wellington da Silva Côrtes

Early‐life experiences critically shape neuroendocrine systems involved in emotional and social behaviours. The oxytocin (OXT) and vasopressin (AVP) systems are particularly sensitive to environmental influences during the perinatal period, a developmental window characterized by high neural plasticity. However, the long‐term effects of perinatal environmental enrichment (PEE) on hypothalamic OXT and AVP neuroplasticity and their relationship with emotional behaviour remain poorly understood. Therefore, this study investigated whether PEE induces persistent behavioural, structural, and neurochemical changes in OXT and AVP neurons in male and female mice. Male and female mice reared in either PEE or non‐enriched environment (NE) conditions were evaluated in adulthood using the elevated plus maze, light/dark box, and sociability/social novelty preference tests. Morphometric analyses assessed soma and nuclear size, as well as OXT and AVP immunoreactivity in neurons of the paraventricular nucleus (PVN) of the hypothalamus. PEE reduced anxiety‐like behaviour, as evidenced by increased open‐arm exploration in the elevated plus maze, particularly in males, and reduced latency to enter the light compartment in the light/dark box. These behavioural effects were accompanied by reduced soma and nuclear dimensions of AVP neurons in PEE males, as well as increased nuclear size and OXT immunoreactivity in both sexes. Correlation analyses showed that smaller AVP neuronal profiles were associated with reduced anxiety‐related behavioural measures, whereas larger OXT neuronal dimensions were associated with reduced risk‐assessment behaviours. Perinatal environmental enrichment induces long‐lasting, sex‐dependent structural and neurochemical plasticity in hypothalamic OXT and AVP systems, which may contribute to the enduring modulation of anxiety‐related behaviours.

Introduction: Isometric strength training (IST) is an important component of different types of sport and others activities of daily life. However, until the present moment, no studies have linked the isometric strength training with acetylcholinesterase (AChE) activity changes. Objective: We evaluated the effects of IST on the muscular AChE activity and strength. Materials and Methods: Wistar rats (n =20) were divided into 2 groups: Control group (Ctr) (sedentary) and trained group (Tr) (submitted to 8 weeks of Isometric strength training). The muscle strength and the acetylcholinesterase activity were evaluated in the solear (SOL) and Extensor Digitorum Longus (EDL) muscles. Results: The body weight of the trained animals was 7.39 % lower than in Ctr rats (p < 0.01) and the EDL weight was 25 % higher (p < 0.05) compared to Ctr. Further, an increase of 30.36 % in strength was observed in the fourth week (p < 0.006) and 26.41 % in eighth week (p < 0.003) of training. In addition, we found an increase of 46.64% in AChE activity in the SOL. In contrast, a reduction of 55.36% in AChE activity in the EDL was observed. Conclusion: Our findings indicate that biochemical, zoometric and functional changes can be evoked by IST with low overload. Keywords: Isometric Strength Training, Solear, Extensor Digitorum Longus and Enzyme.

Highlights Perinatal L-NAME treatment decreased anxiety- and depression-like behaviors in adult mice. Perinatal L-NAME treatment did not promote changes in locomotor activity in adult mice. Perinatal L-NAME treatment did not alter pain perception ABSTRACT Objective: We hypothesized that perinatal manipulations of the nitrergic system would affect adult animal behaviors. Methods: We tested this hypothesis by perinatally administering N(G)-Nitro-L-arginine methyl ester (L-NAME), a non-specific antagonist of nitric oxide synthase for 15 days and assessed anxiety- and depression-like behaviors in adult mice.

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of neonatal treatment of d-fenfluramine (d-FEN), a serotonin (5-HT) releaser, on the behavioral expression of adult male Swiss mice. For this purpose, we divided pregnant female Swiss mice into two groups (n = 6 each and similar to 35 g). Their off-spring were treated with d-FEN (3 mg/kg, s.c.) from postnatal days (PND) 5 to 20. At PND 21, one male puppy of each litter was euthanized; the midbrain and the hippocampus were dissected for RNA analysis. At PND 70, the male off-spring underwent a behavioral assessment in the open field, elevated plus-maze, light-dark box, tail suspension, and rotarod test. The programmed animals had a decrease in 5HT1a, serotonin transporter (SERT), and brain-derived neurotrophic factor (BDNF) expression in the mesencephalic raphe region. Alternatively, there was a reduction only in the tryptophan hydroxylase (TPH2) and BDNF expression in the hippocampus. In the light-dark box test, offspring of the treated group had higher latency to light and less time on the light side than the control. Also, it was observed less time of immobility in the tail suspension test. We also observed low motor skill learning in the rotarod test. These findings suggest that programming with d-FEN during the neonatal period alters a mesencephalic and hippocampal serotonergic system, promoting anxiety, antidepressant behavior, low coordination, and motor learning in adults.

Epidemiological and animal studies have demonstrated a strong association between selenium (Se) supplementation and metabolic disorders, we aimed to evaluate whether maternal Se supplementation was able to change metabolic parameters in rats' offspring. Moreover, as Se is a deiodinase (DIO) cofactor, we decided to investigate how thyroid hormones (THs) would be involved in such metabolic changes. Thereby, two groups (n = 6, ~250 g) of female Wistar rats underwent isotonic saline or sodium selenite (1 mg/kg, p.o.) treatments. Although there were no significant differences in body weight between groups, the Se treatment during pregnancy and lactation increased milk intake and the visceral white adipose tissue (WAT) in offspring. The rats whose mothers were treated with Se also presented an improvement in the glucose tolerance test and in the glucose‐stimulated insulin secretion. Regarding the lipid metabolism, the Se group had a reduction of triglycerides in the liver and in WAT. These metabolic changes were accompanied by an increase in serum triiodothyronine (T₃) and in DIO 2 expression in brown adipose tissue (BAT). We further demonstrate an increased expression of peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha (PGC‐1α) and nuclear respiratory factor‐1 (NRF‐1) mRNA in the liver. In adulthood offspring, Se supplementation programs thyroid function, glucose homeostasis, and feeding behaviour. Taken together, there is no indication that Se programming causes insulin resistance. Moreover, we conjecture that these metabolic responses are induced by increased thyroxine (T₄) to T₃ conversion by DIO2 in BAT and mediated by altered transcription factors expression associated with oxidative metabolism control in the liver.

The development of analgesic drugs is still a necessity due to the inefficiency of the current treatments for some pathological conditions and also due to the adverse effects produced by these drugs. The aim of this study was to deepen the pharmacological study of two new hybrids NSAIDs tetrahydropyran derivatives, regarding their antinociceptive effects on acute pain in mice. Male swiss mice were evaluated in the acetic acid‐induced abdominal writhing, formalin, tail‐flick, open‐field, glutamate‐ and capsaicin‐induced paw licking tests, and in vitro Cox inhibition assay, besides the acute toxicological evaluation. The compounds had an effect on the acetic acid‐induced abdominal writhing, formalin (both phases), and tail‐flick tests. In the study of the mechanism of action was observed reversion of the antinociceptive effect of the compounds from the previous administration of naloxone, L‐NAME (L‐nitro‐arginine methyl ester), ODQ (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one), glibenclamide, and nor‐binaltorphimine, by the intrathecal and intraperitoneal routes. The prior administration of MK‐801 suggests that the modulation of NMDA receptor contributes to the antinociceptive effect of compounds. In summary, hybrid compounds presented central antinociceptive effect, demonstrating participation of the NO‐cGMP‐K⁺ ATP pathway, κ‐opioid, and NMDA receptors. In addition, the compounds showed inhibition of cyclo‐oxygenase enzymes and adverse effects were not observed with dose 300 times greater than the dose used experimentally.