Undernourishment and recurrent seizures early in life impair Long-Term Potentiation and alter NMDAR and AMPAR expression in rat hippocampus.

Undernourishment is a global issue, especially in developing countries, affecting newborns and children in a vulnerable period of brain development. Previous studies of undernourishment models suggested a relationship between undernourishment and epilepsy. The exposure to both undernourishment and recurrent seizures early in life appears to have detrimental effects on the developing brain. This study aims to investigate the neurobiological consequences of undernourishment and recurrent seizures exposure early in life, investigating Long-Term Potentiation (LTP) induction and gene expression of NMDA receptor subunits in the hippocampus during adulthood (P60). Animals were exposed to maternal deprivation protocol from P2 to P15 to control food intake in rat pups and Flurothyl-induced seizures from P7 to P10. Electrophysiological records of hippocampal slices were recorded and gene expression of NR1A, NR2A, NR2B, NR2C, NR2D and BDNF were investigated. Animals exposed to undernourishment or recurrent seizures failed to promote LTP after stimulation. Furthermore, seizure exposure early in life led to increased expression of hippocampal NR1A, NR2A, NR2B, NR2C and NR2D when compared to controls. Interestingly, when animals were exposed to undernourishment paradigm early in life, this upregulation of NDMA subunits was absent. In conclusion, our study showed impaired LTP after undernourishment and recurrent seizures early in life, together with differential expression of NDMA expression in the hippocampus during adulthood.

Dual influences of early life stress induced by limited bedding on walking adaptability and Bdnf/TrkB and Drd1/Drd2 gene expression in different mouse brain regions.

Introduction Evidence suggests early life stress impairs development, quality of life and increases vulnerability to disease. One important aspect of the stress experience is its impact on cognitive-motor performance, which includes the ability to adapt walking according to the environmental conditions. This study aimed to investigate how early-life stress affects walking adaptability of mice, while investigating BDNF/TrkB and Drd1/Drd2 expression in different brain regions. Methods Briefly, we exposed male C56BL/6 to the limited bedding protocol (LB) from post-natal day (PND) 2 to PND9 and then tested animals in the ladder walking task at PND60. RT-qPCR was used to investigate gene expression in the mPFC, hippocampus, motor cortex and cerebellum 2 h after the task Results LB induced a wide range of variability and therefore two distinct subgroups of animals within the LB group were established: a) superior performance (LB-SP); and b) inferior performance (LB-IP), compared to controls. Additionally, Drd1 gene expression was increased in the mPFC of LB-IP animals and in the cerebellum of LB-SP animals, while Drd2 expression was reduced in the hippocampus of the LB-IP group. BDNF exon IV gene expression in the mPFC and motor cortex was increased in both the LB-IP and LB-SP subgroups. TrkB gene expression in the hippocampus was reduced in the LB-IP group. A strong negative correlation was found between walking adaptability performance and BDNF exon IV gene expression in the motor cortex. Conversely, a positive correlation was found between walking adaptability performance and TrkB expression in the mPFC and a negative correlation in the hippocampus. Both Drd1 and Drd2 gene expression were negatively correlated with the ability to adapt walking. Conclusions Overall, our findings suggest exposure to early life stress leads to distinct walking adaptability phenotypes, which may be related to Drd1, Drd2, Bdnf exon IV and TrkB gene expression in brain regions that influence walking adaptability.