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Enhanced Brain-Derived Neurotrophic Factor Signaling in the Nucleus Accumbens of Juvenile Rats

Authors: Brian F. O'Dowd; Theresa Fan; Susan R. George; Melissa L. Perreault;

Enhanced Brain-Derived Neurotrophic Factor Signaling in the Nucleus Accumbens of Juvenile Rats

Abstract

Brain-derived neurotrophic factor (BDNF) signaling through its receptor, tropomyosin receptor kinase B (TrkB), plays a critical role in neural plasticity and its dysregulation in striatum and prefrontal cortex (PFC) has been implicated in the etiology of mental health disorders such schizophrenia and drug addiction. In the present study, we characterized age-dependent differences in BDNF signaling and TrkB expression within the nucleus accumbens (NAc), caudate putamen (CP) and PFC in rats and determined the effects of administration of the dopamine agonist, SKF 83959, which activates the Gq-coupled dopamine receptors, the dopamine D5 receptor and the D1-D2 receptor heteromer. As proBDNF binds with high affinity to the p75 neurotrophin receptor (p75NTR), expression levels of these proteins were also assessed. The present findings showed that juvenile rats (aged 26-28 days) exhibited significantly elevated basal BDNF expression and activation of full-length TrkB (TrkBfull) in NAc compared to their adult counterparts, as evidenced by increased TrkBfull phosphorylation. These changes were concomitant with an increase in the relative expression of TrkBfull compared to the truncated isoform, TrkB.T1, in NAc and CP. Conversely, in PFC the basal expression of BDNF in juvenile rats was significantly lower than in adult rats with an elevated relative expression of TrkBfull. Acute administration of SKF 83959 to juvenile rats abolished the age-dependent differences in BDNF expression in NAc and PFC, and in the relative expression of TrkBfull in NAc and CP. Together these findings indicate that the expression and/or signaling of BDNF and TrkB in striatum and PFC of juvenile rats is fundamentally different from that of adult rats, a finding that may have implications in neuropsychiatric disorders that exhibit age-dependent susceptibility such as schizophrenia and drug addiction.

Keywords

Male, Neurons, Brain-Derived Neurotrophic Factor, Age Factors, Prefrontal Cortex, Receptor, Nerve Growth Factor, Nucleus Accumbens, Rats, Rats, Sprague-Dawley, Dopamine Agonists, Animals, Receptor, trkB, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Caudate Nucleus, Phosphorylation, Signal Transduction

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Average
Average
Top 10%
bronze