Pharmacopsychiatry 2021; 54(05): 205-213
DOI: 10.1055/a-1363-1680
Original Paper

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor

1  Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Germany
2  Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany
3  Leibniz Institute for Neurobiology, Department of Behavioral Neurology, Magdeburg, Germany
4  German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany
,
Golo Kronenberg
2  Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany
5  University of Leicester and Leicestershire Partnership NHS Trust, Leicester, United Kingdom
,
Ulrike Schmidt
1  Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Germany
6  Department of Psychiatry and Psychotherapy, University Medical Center Bonn, Bonn, Germany
,
Henning P. Düsedau
7  Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany
,
Stefanie Ehrentraut
7  Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany
,
Olga Geisel
2  Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany
,
Oliver von Bohlen und Halbach
8  Institute of Anatomy and Cell Biology, Universitätsmedizin Greifswald, Greifswald, Germany
,
Peter Gass
9  Central Institute for Mental Health, Department of Psychiatry and Psychotherapy, Heidelberg University, Mannheim Faculty, Germany
,
Ildiko Rita Dunay
7  Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany
,
Rainer Hellweg
2  Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany
› Author Affiliations
Funding This work was supported by the Deutsche Forschungsgemeinschaft (SFB 779, TP A08, to B.H.S., SFB 854, TP25, to I.R.D., and DFG KR 2591/6–1 to G.K.), and by the State of Saxony-Anhalt and the European Union (Research Alliance “Autonomy in Old Age” to B.H.S. and I.R.D.). The funding agencies had no role in the design, conduction, or interpretation of this work.

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.



Publication History

Received: 27 May 2020
Received: 30 December 2020

Accepted: 12 January 2021

Publication Date:
16 February 2021 (online)

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