Abstract
Background Brain-derived neurotrophic factor (BDNF) exerts its effects
on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB
and the p75 neurotrophin receptor (p75NTR). The latter can promote
inflammation and cell death while TrkB is critically involved in plasticity
and memory, particularly in the hippocampus. Acute and chronic stress have
been associated with suppression of hippocampal BDNF expression and impaired
hippocampal plasticity. We hypothesized that p75NTR might be involved in the
hippocampal stress response, in particular in stress-induced BDNF
suppression, which might be accompanied by increased neuroinflammation.
Method We assessed hippocampal BDNF protein concentrations in
wild-type mice compared that in mice lacking the long form of the p75NTR
(p75NTRExIII−/−) with or without
prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF
concentrations were measured using an optimized ELISA. Furthermore,
whole-brain mRNA expression of pro-inflammatory interleukin-6 (Il6)
was assessed with RT-PCR.
Results Deletion of full-length p75NTR was associated with higher
hippocampal BDNF protein concentration in the stress condition, suggesting
persistently high hippocampal BDNF levels in p75NTR-deficient mice, even
under stress. Stress elicited increased whole-brain Il6 mRNA
expression irrespective of genotype; however,
p75NTRExIII−/− mice showed elevated
baseline Il6 expression and thus a lower relative increase.
Conclusions Our results provide evidence for a role of p75NTR
signaling in the regulation of hippocampal BDNF levels, particularly under
stress. Furthermore, p75NTR signaling modulates baseline but not
stress-related Il6 gene expression in mice. Our findings implicate
p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation
of risk for neuropsychiatric disorders.