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Chronic Mild Unpredictable Stress Selectively Downregulates Exon I Bdnf mRNA in the Rat Frontal Cortex Independently of Anhedonia

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  • Chronic mild unpredictable stress selectively downregulated exon I Bdnf mRNA in the frontal cortex of both anhedonic and resilient rats.
  • BDNF protein levels by ELISA were not significantly altered in frontal cortex, other neocortical regions, hippocampus, or medulla oblongata.
  • Ntrk2 and Ngfr mRNA levels were unchanged, with exons IV, VI, IX unaltered except a tendency for decreased exon IX in anhedonic hippocampus.
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Cell Biochem Funct. 2026 May;44(5):e70225. doi: 10.1002/cbf.70225.

ABSTRACT

Chronic stress is often a precursor to depression. Multiple brain mechanisms underlying the development of depression involve alterations in neurotrophin signaling. In the present study, male Wistar rats were exposed to chronic mild unpredictable stress (CMS), a well-known rodent model of depression, in order to investigate changes in BDNF content, BDNF mRNA expression, and BDNF receptor expression in different brain regions. After 8 weeks of CMS, anhedonia, a symptom of a depressive state, developed in 35% of stressed rats, while 65% remained resilient. The CMS treatment did not significantly affect the BDNF content as measured by ELISA in the frontal cortex, other neocortical regions, the hippocampus, and the medulla oblongata. The levels of exon I Bdnf mRNA decreased in the frontal cortex of both anhedonic and resilient rats. No changes were observed in exons IV, VI and IX in any of the studied brain structures, except for the hippocampus of anhedonic rats, where there was a tendency toward decreased exon IX Bdnf mRNA. The levels of Ntrk2 and Ngfr mRNAs did not significantly change in the brain after CMS. Therefore, the alterations in the expression of exon I Bdnf mRNA observed in this study were caused by chronic stress but were not associated with depression-like anhedonia.

PMID:42117204 | DOI:10.1002/cbf.70225

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