The Molecular Mechanisms Underlying Stress Effects On Hippocampus-dependent Learning And Memory

"Learning and memory" is to acquire outside information and save it in the central nervous system. Stress may impact the process through stress hormones. Hippocampus is an important area participating in different kinds of learning and memory. The function of hippocampus would be influenced by stress due to the widely distributed stress hormone receptors in it. In the hippocampus, information is transmitted through synapses, whose plasticity can be impacted by stress. In some stress-related disorders, such as depression and post-traumatic stress disorder, stress may influence learning and memory via synaptic plasticity. However, the molecular mechanism of stress on synaptic plasticity is not very clear.TDP-43is a nuclear protein, which has been widely studied in frontotemporal lobar degeneration; Rac1, one of the molecular switches in cells, regulates synaptic plasticity; AMPAR, one of the most important glutamate receptors, plays an important role in the synaptic transmission. The investigations indicate that these molecules are involved in learning and memory. It was recently reported that TDP-43might change the trafficking of AMPAR through regulating the transformation of Rac1and Rac1-GTP. To study whether stress impacted learning and memory via TDP-43Rac1-AMPAR pathway, three kinds of stress animal models were established, including aging, chronic stress (repeated stress hormone injection and chronic restraint stress) and acute stress (foot shock). Western blot results indicated that aging down-regulated the expression of TDP-43, Rac1and AMPAR subunit GluR2, acute foot shock only decreased the expression of GluR2, while repeated stress hormone injection and chronic restraint stress up-regulated the expression of GluR2.In summary, the three types of stress had different effects on the TDP-43-Rac1-AMPAR pathway. Aging had the most profound effect on the pathway, acute foot shock only influenced the downstream of the pathway, and the up-regulation of GluR2by chronic stress might be a compensatory mechanism. Our investigations have provided preliminary results for the exploration of molecular mechanism underlying stress effects on hippocampus-dependent learning and memory.