Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1

• DOI: 10.1073/pnas.1016424108
• Publication Date: 2011-01-05T01:45:06Z
• Authors: Shusaku Uchida; Kumiko Hara; Ayumi Kobayashi; Mitsuaki Fujimoto; Koji Otsuki; Hirotaka Yamagata; Teruyuki Hobara; Naoko Abe; Fumihiro Higuchi; Tomohiko Shibata; Shunsuke Hasegawa; Satoshi Kida; Akira Nakai; Yoshifumi Watanabe
• Keywords: HSF1; Subgranular zone

Aberrant transcriptional regulation in the brain is thought to be one of key components pathogenesis and pathophysiology neuropsychiatric disorders. Heat shock factors (HSFs) modulate cellular homeostasis through control gene expression. However, roles HSFs function have yet elucidated fully. In present study, we attempted clarify role HSF1-mediated neuronal behavioral development using HSF1-deficient (HSF1 −/− ) mice. We found granule neurons aberrant morphology impaired neurogenesis dentate gyrus HSF1 addition, mice showed affective behavior, including reduced anxiety sociability but increased depression-like behavior aggression. Furthermore, deficiency enhanced vulnerability repeated exposure restraint stress. Importantly, rescuing neonatal not adult hippocampus reversed behaviors. These results indicate a crucial for hippocampal development. Analysis molecular mechanisms revealed that directly modulates expression polysialyltransferase genes, which then polysialic acid–neural cell adhesion molecule (PSA-NCAM) levels hippocampus. Enzymatic removal PSA from resulted during adulthood, similar observed Thus, these suggest PSA-NCAM polysialyltransferases, process might involved