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.
Highlights
BDNF2 and neurotrophin-3 (NT-3) are widely distributed in the adult CNS and exhibit unique functions in particular
When the levels at ZT6 were normalized to 100% at any age, brain-derived neurotrophic factor (BDNF) levels at ZT18 significantly increased in the three brain regions of 14-day-old rats but not 7- or 21-day-old rats, (*, p Ͻ 0.05; **, p Ͻ 0.01 by the Student’s t test)
This study shows that diurnal variations in BDNF concentration, high in the dark phase and low in the light phase, are age-dependently acquired in specific brain regions
Summary
Regarding the effects of an abnormal LD cycle, a phase advance of the cycle decreases BDNF levels in a majority of brain regions in adult rats 1 week after treatment, leading to depression of neuronal activity (8). We found evidence for diurnal variation in BDNF levels in a majority of brain regions from 14-day-old rats and an inverse variation of NT-3 levels in the NCX as well as in the visual cortex (VCX). We first examined the effects of an abnormal LD cycle or of a disturbed sleep-wake cycle on BDNF and NT-3 levels and on synaptophysin expression in the NCX of rat pups. Because sleep and circadian rhythm disruption is frequently observed in patients with psychiatric disorders and neurodegenerative diseases (13), we investigated alterations of the diurnal rhythms of BDNF and NT-3 levels and synaptophysin expression in mutant mice with abnormal sleepwake cycles and compared them with controls. We report that alteration of BDNF and NT-3 levels and/or perturbation in diurnal rhythms of their levels reduces synaptophysin-positive presynaptic terminals in layer IV of the NCX of juvenile rats
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
