title: 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.
abstract: 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 Ca(2+)-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.
authors.affiliation: Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Hamatake
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyazaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Sudo
authors.forename: Motoko
authors.initials: M
authors.lastname: Matsuda
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Sadakata
authors.forename: Asako
authors.initials: A
authors.lastname: Furuya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichisaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hata
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakagawa
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Nagata
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Katoh-Semba
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008959:Models, Neurological; D020933:Neurotrophin 3 / Q000378:metabolism*; D017440:Photoperiod; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium