Postweaning Enriched Environment Enhances Cognitive Function and Brain-Derived Neurotrophic Factor Signaling in the Hippocampus in Maternally Separated Rats.

Adverse environments during early life may lead to different neurophysiological and behavioral consequences, including depression and learning and memory deficits that persist into adulthood. Previously, we demonstrated that exposure to an enriched environment during adolescence mitigates the cognitive impairment observed after maternal separation in a task-specific manner. However, underlying neural mechanisms are still not fully understood. The current study examines the effects of neonatal maternal separation (MS) and postweaning environmental enrichment (EE) on spatial learning and memory performance in a short version of the Barnes Maze, active and passive behaviors in the forced swim test, and on TrkB/BDNF receptor expression in the hippocampus. Our results revealed that MS impaired acquisition learning and that enriched rats performed better than non-enriched rats in acquisition trials, regardless of early conditions. During the probe, enriched-housed rats demonstrated better performance than those reared in standard conditions. No significant differences between groups were found in the forced swim test. Both MS and EE increase full-length TrkB expression, and the combination of MS and EE treatment caused the highest levels of this protein expression. Similarly, truncated TrkB expression was higher in the MS/EE group. Animal facility rearing (AFR) non-enriched groups present the lowest activation of phosphorylated Erk, a canonical downstream kinase of TrkB signaling. Taken together, our results demonstrate the importance of enriched environment as an intervention to ameliorate the effects of maternal separation on spatial learning and memory. TrkB/BDNF signaling could mediate neuroplastic changes related to learning and memory during exposure to enriched environment.

Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice.

Growth hormone secretagogue receptor (GHSR), the receptor for ghrelin, is expressed in key brain nuclei that regulate food intake. The dopamine (DA) pathways have long been recognized to play key roles mediating GHSR effects on feeding behaviors. Here, we aimed to determine the role of GHSR in DA neurons controlling appetitive and consummatory behaviors towards high fat (HF) diet. For this purpose, we crossed reactivable GHSR-deficient mice with DA transporter (DAT)-Cre mice, which express Cre recombinase under the DAT promoter that is active exclusively in DA neurons, to generate mice with GHSR expression limited to DA neurons (DAT-GHSR mice). We found that DAT-GHSR mice show an increase of c-Fos levels in brain areas containing DA neurons after ghrelin treatment, in a similar fashion as seen in wild-type mice; however, they did not increase food intake or locomotor activity in response to systemically- or centrally-administered ghrelin. In addition, we found that satiated DAT-GHSR mice displayed both anticipatory activity to scheduled HF diet exposure and HF intake in a binge-like eating protocol similar to those in wild-type mice, whereas GHSR-deficient mice displayed impaired responses. We conclude that GHSR expression in DA neurons is sufficient to both mediate increased anticipatory activity to a scheduled HF diet exposure and fully orchestrate binge-like HF intake, but it is insufficient to restore the acute orexigenic or locomotor effects of ghrelin treatment. Thus, GHSR in DA neurons affects appetitive and consummatory behaviors towards HF diet that take place in the absence of caloric needs.

Multiparity Dampened the Neurobehavioral Consequences of Mother-Pup Separation Stress in Dams.

Reproductive experience in mammals produces significant neuroendocrine and behavioral changes that are necessary to ensure the survival of the mother and the young. Exposure to stress during postpartum may affect the proper development of maternal behaviors. The present study examined whether previous reproductive experience affects neurobehavioral responses in females exposed to mother-infant separation stress during the postpartum period (4.5 h/day for 3 weeks). Anxiety-like behavior and spatial learning were evaluated in nulliparous (NP), primiparous (PRI) and multiparous (MULT). In maternal animals (PRI and MULT), maternal behavior was also assessed. Cell survival and proliferation in the dentate gyrus, as well as BDNF expression in the hippocampus, were evaluated by immunohistochemistry as possible candidates for mediating brain plasticity in response to reproductive experience and stress. Anxiety-like behavior as measured on the open field test showed an increase in NP and PRI-stressed, while neither stressed nor unstressed MULT expressed this behavior. Maternal unstressed animals both PRI and MULT exhibited enhanced memory task performance in the Barnes maze. Multiparity increased cell proliferation and cell survival in female rats and these changes occurred independently of pup exposure. The expression of BDNF was higher in the CA1 area in MULT rats. Although multiparity protects the mother against some of the effects of maternal separation stress, promoting behaviors directed to the pups during the early postpartum, preventing anxiety-like behaviors and mitigating memory deterioration after weaning, the data showed that disrupting natural dam-pup interaction produced neurobiological consequences on the mother even with multiple reproductive experience.

Early maternal separation: neurobehavioral consequences in mother rats.

Repeated separation of dams from their pups during the postpartum period may evoke emotional stress in the dam. In the present study we investigated whether prolonged maternal separation is stressful for rat dams by studying different behavioral and central responses known to be affected by stress. After delivery, female Wistar rats were subjected to either animal facility rearing (AFR) conditions or daily 4.5 h of mother-litter separation from postpartum day (PPD) 1-21. Maternal care (pup retrieval) was evaluated at PPD 3. After weaning on PPD 21, anxiety (elevated plus maze) and depression-like behaviors (forced swimming test) were assessed in the dams. Memory abilities (one-trial step down inhibitory avoidance) were tested either 1 h (short-term memory) or 24 h (long-term memory) after training session. Finally, c-Fos expression was examined in the central nucleus of the amygdala. The results revealed that pup retrieval efficiency at PPD 3 was significantly impaired by maternal separation. AFR dams retrieved their pups sooner and engaged in more pup-directed activities (nest building and carrying pups). Separation from pups increased the number of entries in open arms of the plus maze and decreased latency times in the inhibitory avoidance test for both short and long-term memory in the dams. There were no differences in depression-related behavior as assessed using the forced swimming test. Furthermore, maternal separation yielded high c-Fos expression in the central nucleus of the amygdala. Together, these data indicate that repeated maternal separation in the early postpartum period reduces maternal care and impairs the retention memory, providing further evidence for the detrimental neurobehavioral effects of maternal separation in dams.