Hippocampal BDNF mRNA shows a diurnal regulation, primarily in the exon III transcript.

Endogenous expression levels of brain-derived neurotrophic factor (BDNF) mRNA were assessed using in situ hybridization to investigate whether there is a natural diurnal fluctuation in BDNF mRNA expression in the hippocampus of rats housed with a normal (12:12 h) light/dark cycle. BDNF expression was increased during lights out (dark-cycle) to 134%-158% of light-cycle levels in hippocampal regions CA1, CA3, and hilus. In addition, expression levels of the four BDNF transcript forms, exons I-IV, were assessed to evaluate whether expression of specific BDNF transcripts exhibited differential endogenous fluctuation. All exons had lowest levels of expression at either noon or 6 p.m. Significant correlations were found between exon expression level and time, with elevated expression occurring at dark-cycle timepoints. The exon III transcript showed the greatest diurnal change in expression in all hippocampal fields, with dark-cycle expression elevated to 219-419% of light-cycle expression level. In addition to exon III, dark-cycle exon II mRNA levels were elevated in all hippocampal subfields, to 140-180% of light-cycle levels, suggesting that the endogenous fluctuation in BDNF expression results predominantly from activation of the promoters linked to exons II and III. Previously we have shown that physical activity increases BDNF expression. The naturally occurring rise in BDNF expression during the dark-cycle, the time when rats are most physically active, may be due to increased activity and arousal levels. Because BDNF has a role in plasticity, the increase in BDNF expression during the time that a rat is maximally interacting with its surroundings may be part of an ongoing stimulus-encoding mechanism, or may be a mechanism to maximize information storage about the environment.