Increased hippocampal CREB phosphorylation after retrieval of remote contextual fear memories in Carioca high-conditioned freezing rats.

The participation of the hippocampal formation in consolidation and reconsolidation of contextual fear memories has been widely recognized and known to be dependent on the activation of the cAMP response element (CRE) binding protein (CREB) pathway. Recent findings have challenged the prevailing view that over time contextual fear memories migrate to neocortical circuits and no longer require the hippocampus for retrieval of remote fearful memories. It has also recently been found that this brain structure is important for the maintenance and recall of remote fear memories associated with aversive events, a common trait in stress-related disorders such as generalized anxiety disorder (GAD), major depression, and post-traumatic stress disorder. In view of these findings, here we examined the putative role of CREB in the hippocampus of an animal model of GAD during the retrieval of remote contextual fear memories. Specifically, we evaluated CREB phosphorylation in the hippocampus of male Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively) upon re-exposure of animals to contextual cues associated to footshocks weeks after fear conditioning. Age-matched male rats from a randomized crossbreeding population served as controls (CTL). Adrenal catecholamine levels were also measured as a biological marker of stress response. Seven weeks after contextual fear conditioning, half of the sample of CHF (n = 9), CLF (n = 10) and CTL (n = 10) rats were randomly assigned to return to the same context chamber where footshocks were previously administrated (Context condition), while the remaining animals were individually placed in standard housing cages (Control condition). Western blot results indicated that pCREB levels were significantly increased in the hippocampus of CHF rats for both Context and Control conditions when compared to the other experimental groups. CHF rats in the Context condition also exhibited significant more freezing than that observed for both CLF and CTL rats. Lastly, CHF animals in the Context condition displayed significantly higher adrenal catecholamine levels than those in the Control condition, whereas no differences in catecholamine levels were observed between Context and Control conditions for CLF and CTL rats. These findings are discussed from a perspective in which the hippocampus plays a role in the maintenance and recall of remote contextual fear memories via the CREB pathway.

Maternal protein restriction during the lactation period disrupts the ontogenetic development of behavioral traits in male Wistar rat offspring.

Neonatal undernutrition in rats results in short- and long-term behavioral and hormonal alterations in the offspring. It is not clear, however, whether these effects are present since the original insult or if they develop at some specific age later in life. Here, we assessed the ontogenetic profile of behavioral parameters associated with anxiety, exploration and memory/learning of Wistar rat offspring that were subjected to protein malnutrition during lactation. Dams and respective litters were separated into two groups: (1) protein-restricted (PR), which received a hypoproteic chow (8% protein) from birth to weaning [postnatal day (PN) 21]; (2) control (C), which received normoproteic chow. Offspring's behaviors, corticosterone, catecholamines, T3 and T4 levels were assessed at PN21 (weaning), PN45 (adolescence), PN90 (young adulthood) or PN180 (adulthood). PR offspring showed an age-independent reduction in the levels of anxiety-like behaviors in the Elevated Plus Maze and better memory performance in the Radial Arm Water Maze. PR offspring showed peak exploratory activity in the Open Field earlier in life, at PN45, than C, which showed theirs at PN90. Corticosterone was reduced in PR offspring, particularly at young adulthood, while catecholamines were increased at weaning and adulthood. The current study shows that considerable age-dependent variations in the expression of the observed behaviors and hormonal levels exist from weaning to adulthood in rats, and that protein restriction during lactation has complex variable-dependent effects on the ontogenesis of the assessed parameters.

Innovative treatments for epilepsy: Venom peptides, cannabinoids, and neurostimulation.

Antiepileptic drugs have been successfully treating epilepsy and providing individuals sustained seizure freedom. However, about 30% of the patients with epilepsy present drug resistance, which means they are not responsive to the pharmacological treatment. Considering this, it becomes extremely relevant to pursue alternative therapeutic approaches, in order to provide appropriate treatment for those patients and also improve their quality of life. In the light of that, this review aims to discuss some innovative options for the treatment of epilepsy, which are currently under investigation, addressing strategies that go from therapeutic compounds to clinical procedures. For instance, peptides derived from animal venoms, such as wasps, spiders, and scorpions, demonstrate to be promising antiepileptic molecules, acting on a variety of targets. Other options are cannabinoids and compounds that modulate the endocannabinoid system, since it is now known that this network is involved in the pathophysiology of epilepsy. Furthermore, neurostimulation is another strategy, being an alternative clinical procedure for drug-resistant patients who are not eligible for palliative surgeries.

Current knowledge, challenges, new perspectives of the study, and treatments of Autism Spectrum Disorder.

Over the past 70 years, the understanding of Autism Spectrum Disorder (ASD) improved greatly and is characterized as a heterogeneous neuropsychiatric syndrome. ASD is characterized by difficulties in social communication, restricted and repetitive behavior, interests, or activities. And it is often described as a combination of genetic predisposition and environmental factors. There are many treatments and approaches to ASD, including pharmacological therapies with antipsychotics, antidepressants, mood regulators, stimulants, and behavioral ones. However, no treatment is capable of reverting ASD. This review provides an overview of animal models of autism. We summarized genetic and environmental models and then valproic acid treatment as a useful model for ASD. As well as the main therapies and approaches used in the treatment, relating them to the neurochemical pathways altered in ASD, emphasizing the pharmacological potential of peptides and bioinspired compounds found in animal venoms as a possible future treatment for ASD.