Early-life stress affects behavioral and neurochemical parameters differently in male and female juvenile Wistar rats.

Neonatal handling is an early life stressor that leads to behavioral and neurochemical changes in adult rats in a sex-specific manner and possibly affects earlier stages of development. Here, we investigated the effects of neonatal handling (days 1-10 after birth) on juvenile rats focusing on biochemical parameters and olfactory memory after weaning. Male neonatal handled rats performed more crossings on the hole-board task, increased Na+ /K+ -ATPase activity in the olfactory bulb, and decreased acetylcholinesterase activity in the hippocampus versus non-handled males. Female neonatal handled animals increased the number of rearing and nose-pokes on the hole-board task, decreased glutathione peroxidase activity, and total thiol content in the hippocampus versus non-handled females. This study reinforces that early life stress affects behavioral and neurochemical parameters in a sex-specific manner even before the puberty onset.

Preventive and therapeutic effects of environmental enrichment in Wistar rats submitted to neonatal hypoxia-ischemia.

Environmental enrichment (EE) at early stages of neurodevelopment attenuates HI-induced behavioral, histological and cellular damage. However, the effects of EE exposure during gestational or early postnatal period and the possible influence of sexual dimorphism on EE protection are not fully understood. Present study evaluated the effects of pre-natal and postnatal EE, as well as their combination, in male and female rats submitted to neonatal HI at postnatal day (PND) 3. Wistar rats were housed in EE or in standard condition (SC) during all pregnancy. At PND1, the litters were randomly allocated to the same prenatal environment during lactation (SC + SC or EE + EE) or housed in a new environment until weaning (SC + EE or EE + SC). Behavioral tasks were performed from PND 60-75. Then, animals were euthanized for biochemical and histological analysis. Prenatal and early postnatal EE alone improved performance of HI males in the Water Maze spatial memory task, while HI females were most benefited from early postnatal stimulation. Moreover, EE attenuated HI-induced lower anxiety-like behavior in rats of both sexes and decreased hyperlocomotion in HI females. Hippocampus tissue preservation and higher VEGF and TrkB levels were observed in all HI groups exposed to EE. Interestingly, HI males exposed to prenatal or postnatal EE alone exhibited higher GFAP levels and additional tissue preservation. Therefore, both prenatal and early postnatal environmental enrichment cause attenuation of HI-induced impairments, revealing their preventive and therapeutic actions, possibly due to VEGF and astrocyte activity; some of these effects are sex-specific.

Locomotor Training Promotes Time-dependent Functional Recovery after Experimental Spinal Cord Contusion.

Locomotor training (LT) has been exhaustively investigated as a treatment for the spinal cord injury (SCI), however the literature reports both positive and negative effects over the functional recovery. The initiation period of LT following SCI is one of the major variables that needs attention. To investigate the better period, three different starting times were investigated after SCI in rats. Methods: Wistar rats were randomly divided into groups: control, SCI (rats with spinal cord contusion), and SCI groups exposed to LT starting 7, 14 or 28 days after the injury (SCI-T7, SCI-T14 and SCI-T28). LT was performed on a treadmill, five days a week, 20 minutes per day, for ten weeks. Basso, Breattie and Bresnahan (BBB) scale and Horizontal Ladder walking test were used to evaluate the motor function; at the end, morphological and biochemical analyses of the spinal cords, tibialis anterior and soleus muscles were performed. Results: SCI-T14 and SCI-T28 groups had an improvement in both behavioral tests, while SCI-T7 presented a worsening in the functional performance. Late training groups preserved motoneurons in the spinal cord, showed larger muscle fiber areas and higher BDNF expression in tibialis anterior muscle. SCI-T7 group had higher lesion volume after LT in comparison with the SCI group. Late onset of LT promoted an increment of the hindlimb function, while early onset of training worsened the functional recovery of the SCI animals. These results demonstrate a critical LT starting time after the injury, contributing to define the best therapeutic window for rehabilitation.

Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.

Energy drinks and their component modulate attention, memory, and antioxidant defences in rats.

PURPOSE: This study aimed to evaluate the effects of the subchronic consumption of energy drinks and their constituents (caffeine and taurine) in male Wistar rats using behavioural and oxidative measures. METHODS: Energy drinks (ED 5, 7.5, and 10 mL/kg) or their constituents, caffeine (3.2 mg/kg) and taurine (40 mg/kg), either separately or in combination, were administered orally to animals for 28 days. Attention was measured though the ox-maze apparatus and the object recognition memory test. Following behavioural analyses, markers of oxidative stress, including SOD, CAT, GPx, thiol content, and free radicals, were measured in the prefrontal cortex, hippocampus, and striatum. RESULTS: The latency time to find the first reward was lower in animals that received caffeine, taurine, or a combination of both (P = 0.003; ANOVA/Bonferroni). In addition, these animals took less time to complete the ox-maze task (P = 0.0001; ANOVA/Bonferroni), and had better short-term memory (P < 0.01, Kruskal-Wallis). The ED 10 group showed improvement in the attention task, but did not differ on other measures. In addition, there was an imbalance in enzymatic markers of oxidative stress in the prefrontal cortex, the hippocampus, and the striatum. In the group that received both caffeine and taurine, there was a significant increase in the production of free radicals in the prefrontal cortex and in the hippocampus (P < 0.0001; ANOVA/Bonferroni). CONCLUSIONS: Exposure to a combination of caffeine and taurine improved memory and attention, and led to an imbalance in the antioxidant defence system. These results differed from those of the group that was exposed to the energy drink. This might be related to other components contained in the energy drink, such as vitamins and minerals, which may have altered the ability of caffeine and taurine to modulate memory and attention.

Isolation stress exposure and consumption of palatable diet during the prepubertal period leads to cellular changes in the hippocampus.

Social isolation is one of the most potent stressors in the prepubertal period and may influence disease susceptibility or resilience in adulthood. The glucocorticoid response and, consequently, the adaptive response to stress involve important changes in mitochondrial functions and apoptotic signaling. Previous studies have shown that consumption of a palatable diet reduces some stress effects. Therefore, the aim of the present study was to investigate whether isolation stress in early life can lead to cellular alterations in the hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage index, mitochondrial mass and potential, respiratory chain enzyme activities, apoptosis, and necrosis in the hippocampus of juvenile male rats submitted or not to isolation stress during the pre-puberty period. We also verified whether consumption of a palatable diet during this period can modify stress effects. Results show that stress led to an oxidative imbalance, DNA breaks, increased the mitochondrial potential and early apoptosis, and decreased the number of live and necrotic cells. In addition, the palatable diet increased glutathione peroxidase activity, high mitochondrial potential and complex I-III activity in the hippocampus of juvenile rats. The administration of a palatable diet during the isolation period prevented the stress effects that caused the reduction in live cells and increased apoptosis. In conclusion, the stress experienced during the pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage, mitochondrial dysfunction, and increased apoptosis, while consumption of a palatable diet attenuated some of these effects of exposure, such as the reduction in live cells and increased apoptosis, besides favoring an increase in antioxidant enzymes activities.

Isolation stress during the prepubertal period in rats induces long-lasting neurochemical changes in the prefrontal cortex.

Social isolation during postnatal development leads to behavioral and neurochemical changes, and a particular susceptibility of the prefrontal cortex to interventions during this period has been suggested. In addition, some studies showed that consumption of a palatable diet reduces some of the stress effects. Therefore, our aim is to investigate the effect of isolation stress in early life on some parameters of oxidative stress and energy metabolism (Na(+),K(+)-ATPase activity, respiratory chain enzymes activities and mitochondrial mass and potential) in prefrontal cortex of juvenile and adult male rats. We also verified if the consumption of a palatable diet during the prepubertal period would reduce stress effects. The results showed that, in juvenile animals, isolation stress increased superoxide dismutase and Complex IV activities and these effects were still observed in the adulthood. An interaction between stress and diet was observed in catalase activity in juveniles, while only the stress effect was detected in adults, reducing catalase activity. Access to a palatable diet increased Na(+),K(+)-ATPase activity in juveniles, an effect that was reversed after removing this diet. On the other hand, isolation stress induced a decreased activity of this enzyme in adulthood. No effects were observed on glutathione peroxidase, total thiols and free radicals production, as well as on mitochondrial mass and potential. In conclusion, isolation stress in the prepubertal period leads to long-lasting changes on antioxidant enzymes and energetic metabolism in the prefrontal cortex of male rats, and a palatable diet was not able to reverse these stress-induced effects.