Virtual Conference
Neuroscience conference 2022

Yoshinori Takei

Toho University, Japan

Title: Vagal nerve-mediated expression of brain-derived neurotrophic factor induced by the intraperitoneal administration of a chemokine CX3CL1

Abstract

Functional deficiency in brain derived neurotrophic factor (BDNF) is frequently observed in the brain of patients not only with Alzheimer’s disease but also with psychiatric diseases, such as depression, schizophrenia, and bipolar disorder. Moreover, the deficiency is proposed as a reason for age-dependent decline in cognitive function in healthy older adults. The exogenous application of BDNF has been explored as a potential therapeutic approach; however, it revealed several limitations. Therefore, methods to promote BDNF synthesis in the brain are needed to be developed. Exercise is known to induce expression of BDNF in the brain of older adults and increase the expression of a chemokine CX3CL1 in peripheral tissues. CX3CL1 is a chemokine that chemoattracts T cells and monocytes. It promotes survival of neurons in the brain and ?-cells in the pancreas. In adipose tissues, it is expressed in adipocytes and attenuates effects of obesity-induced chronic inflammation. However, effects of CX3CL1 on the BDNF expression was unknown. Recently, we found that intraperitoneal administration of CX3CL1 augmented BDNF expression in the hippocampus of aged mice. CX3CL1 not only reversed the age-associated accumulation of cells expressing the senescence marker p16INK4a but also increased peritoneal phagocytic activity, indicating that CX3CL1 affected the phenotypes of peritoneal cells. In the hippocampus of aged mice, CX3CL1 increased the number of Type-2 neural stem cells and promoted BDNF expression. This treatment, furthermore, improved novel object recognition memory impaired with advancing age. Intraperitoneal transplantation of peritoneal cells from CX3CL1-treated aged mice improved novel object recognition memory in recipient aged mice. Vagotomy inhibited the CX3CL1-induced increase in BDNF expression. Thus, our results indicate that CX3CL1 administered into the peritoneal cavity promote the BDNF level in the hippocampus in aged mice, via peritoneal cells and the vagal nerve.


Biography

Yoshinori Takei has completed his PhD from Technology Institute of Tokyo (Japan) and postdoctoral studies from Cambridge University and Medical Research Council in United Kingdom. He is an associate professor of faculty of medicine, Toho University.