TY  - JOUR
AU  - Schott, Björn
AU  - Kronenberg, Golo
AU  - Schmidt, Ulrike
AU  - Düsedau, Henning P
AU  - Ehrentraut, Stefanie
AU  - Geisel, Olga
AU  - von Bohlen Und Halbach, Oliver
AU  - Gass, Peter
AU  - Dunay, Ildiko Rita
AU  - Hellweg, Rainer
TI  - Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor.
JO  - Pharmacopsychiatry
VL  - 54
IS  - 5
SN  - 1439-0795
CY  - Stuttgart [u.a.]
PB  - Thieme
M1  - DZNE-2021-00803
SP  - 205-213
PY  - 2021
AB  - 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.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.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.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.
KW  - Animals
KW  - Brain-Derived Neurotrophic Factor: genetics
KW  - Brain-Derived Neurotrophic Factor: metabolism
KW  - Hippocampus: metabolism
KW  - Mice
KW  - Receptor, Nerve Growth Factor: metabolism
KW  - Receptors, Nerve Growth Factor: genetics
KW  - Receptors, Nerve Growth Factor: metabolism
KW  - Signal Transduction
LB  - PUB:(DE-HGF)16
C6  - pmid:33592642
DO  - DOI:10.1055/a-1363-1680
UR  - https://pub.dzne.de/record/155635
ER  -