Activation of brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling in the pedunculopontine tegmental nucleus: a novel mechanism for the homeostatic regulation of rapid eye movement sleep.

摘要: Rapid eye movement (REM) sleep dysregulation is a symptom of many neuropsychiatric disorders, yet the mechanisms REM homeostatic regulation are not fully understood. We have shown that, after deprivation, pedunculopontine tegmental nucleus (PPT) plays critical role in generation recovery sleep. In this study, we used multidisciplinary techniques to show causal relationship between brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling PPT and development drive. Rats were randomly assigned conditions unrestricted or selective deprivation (RSD) with microinjections vehicle control dose TrkB inhibitor (2, 3, 4 nmol K252a ANA-12). On experimental days, rats received their sleep-wake physiological signals recorded for 3 6 h, during which RSD was performed first h. At end all h recordings, killed dissected out BDNF quantification. Our results that ANA-12 dose-dependently reduced responses RSD. Specifically, inhibition drive limited rebound. There also dose-dependent suppression up-regulation, regression analysis revealed significant positive level expression. These data provide direct evidence activation BDNF-TrkB step