Short-term Heat Exposure Promotes Hippocampal Neurogenesis via Activation of Angiotensin II Type 1 Receptor in Adult Rats

Angiotensin II (Ang II) synthesized in response to body fluid loss caused by actions such as sweating and breathing is today considered as one of the essential factors for promoting hippocampal neurogenesis. Because heat stimuli, along with exercise, increase systemic levels of Ang II, the effects of short-term heat exposure on hippocampal neurogenesis were examined in adult male rats. When rats were exposed daily to a 1-h heat treatment (36.0 ± 0.1 °C) during a 7-d experimental period, the number of doublecortin-immunoreactive newborn cells in the hippocampal dentate gyrus was increased approximately 1.4-fold compared with that in controls that were exposed to a normothermic environment (25.0 ± 0.8 °C). No significant change was observed in the number of Ki-67-immunoreactive stem cells. Western blot and immunohistochemical analyses revealed an enhancement of vascular endothelial growth factor (VEGF) expression in hippocampal astrocytes following short-term heat exposure. These beneficial effects of short-term heat exposure were prevented when an antagonist for Ang II type 1 receptor (AT1R), candesartan, was given orally. These results indicate that short-term heat exposure enhances adult neurogenesis via activation of AT1R in the hippocampal dentate gyrus, in which VEGF may participate by promoting cell proliferation and/or newborn neuron survival.