Phase Advance of the Light-Dark Cycle Perturbs Diurnal Rhythms of Brain-derived Neurotrophic Factor and Neurotrophin-3 Protein Levels, Which Reduces Synaptophysin-positive Presynaptic Terminals in the Cortex of Juvenile Rats

• Published in: The Journal of biological chemistry Vol. 286; no. 24; pp. 21478 - 21487
• Main Authors: Hamatake, Michiko, Miyazaki, Noriko, Sudo, Kaori, Matsuda, Motoko, Sadakata, Tetsushi, Furuya, Asako, Ichisaka, Satoshi, Hata, Yoshio, Nakagawa, Chiaki, Nagata, Koh-ichi, Furuichi, Teiichi, Katoh-Semba, Ritsuko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.06.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Akt PKB; Animals; BDNF; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Calcium - metabolism; Cerebral Cortex - metabolism; Gene Expression Regulation; Male; Mice; Models, Neurological; Neurobiology; Neurodevelopment; Neurotrophic Factor; Neurotrophin; Neurotrophin 3 - metabolism; NT-3; Photoperiod; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Synapses; Synapses - metabolism; Neurotrophin; BDNF; Neurodevelopment; NT-3; Akt PKB; Neurotrophic Factor; Synapses
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.195859

In adult rat brains, brain-derived neurotrophic factor (BDNF) rhythmically oscillates according to the light-dark cycle and exhibits unique functions in particular brain regions. However, little is known of this subject in juvenile rats. Here, we examined diurnal variation in BDNF and neurotrophin-3 (NT-3) levels in 14-day-old rats. BDNF levels were high in the dark phase and low in the light phase in a majority of brain regions. In contrast, NT-3 levels demonstrated an inverse phase relationship that was limited to the cerebral neocortex, including the visual cortex, and was most prominent on postnatal day 14. An 8-h phase advance of the light-dark cycle and sleep deprivation induced an increase in BDNF levels and a decrease in NT-3 levels in the neocortex, and the former treatment reduced synaptophysin expression and the numbers of synaptophysin-positive presynaptic terminals in cortical layer IV and caused abnormal BDNF and NT-3 rhythms 1 week after treatment. A similar reduction of synaptophysin expression was observed in the cortices of Bdnf gene-deficient mice and Ca2+-dependent activator protein for secretion 2 gene-deficient mice with abnormal free-running rhythm and autistic-like phenotypes. In the latter mice, no diurnal variation in BDNF levels was observed. These results indicate that regular rhythms of BDNF and NT-3 are essential for correct cortical network formation in juvenile rodents.