A phase advance of the light‐dark cycle stimulates production of BDNF, but not of other neurotrophins, in the adult rat cerebral cortex: association with the activation of CREB

Abstract

Circadian variation in the expression of brain‐derived neurotrophic factor (BDNF) indicates that BDNF is involved in the regulation of diurnal rhythms in a variety of biological processes. However, it is still unclear which brain regions alter their BDNF levels in response to external light input. Therefore, in selected brain regions of adult male rats, we investigated diurnal variation, as well as the effects of a single eight‐hour phase advance of the light‐dark cycle, on the levels of BDNF and of other neurotrophins. The cerebellum, hippocampus and cerebral cortex containing visual cortex (VCX) showed diurnal variation in BDNF protein levels and the VCX also in NT‐3 levels. In the VCX and the region containing the entorhinal cortex and amygdala (ECX), BDNF protein levels were increased 12 h after the phase advance, while BDNF mRNA levels were increased significantly in the VCX and slightly in the ECX after 4 h. After one week, however, BDNF protein levels were reduced in eight brain regions out of 13 examined. BDNF levels in the ECX and VCX were significantly different between light rearing and dark rearing, while a hypothyroid status did not produce an effect. Cyclic AMP responsive element‐binding protein (CREB), a transcription factor for BDNF, was greatly activated by the phase advance in the ECX and VCX, suggesting the existence of CREB‐mediated pathways of BDNF synthesis that are responsive to external light input.

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

“…Modification of the Rearing Environment-A single 8-h phase advance of the LD cycle was achieved using procedures similar to those previously reported for adult rats (8). The advance was started at 23:00 on postnatal day 6.…”

“…Analyses of Active Protein Kinases-Active Akt and ERK1/2 in the NCX were analyzed as described previously (8). Briefly, homogenates of the NCX were applied to 10% SDS gels.…”

“…NT-3 levels in the NCX-It has been reported that, in specific brain regions of adult rats, an 8-h phase advance of the LD cycle causes an increase or decrease in BDNF concentrations after a 12-h rearing or a 1-week rearing, respectively (8). Therefore, we carried out similar experiments using juvenile rats (Fig.…”

“…Recently, it has been reported that BDNF is expressed rhythmically according to the light-dark (LD) cycle in the cerebellum (Cbl), the hippocampus (Hip), and the cerebral neocortex (NCX) as well as the suprachiasmatic nucleus (SCN) in adult rats (3)(4)(5)(6)(7)(8). In particular, BDNF in the NCX oscillates with a unique cycle, suggesting that neurons are still active in the sleeping phase (8). 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).…”

“…In particular, BDNF in the NCX oscillates with a unique cycle, suggesting that neurons are still active in the sleeping phase (8). 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). Moreover, it has been shown that chronic jet lag leads to atrophy of the human temporal cortex and that light deprivation damages monoamine neurons, producing a depressive behavioral phenotype in rats (9,10).…”