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

Björn H. Schott; Golo Kronenberg; Ulrike Schmidt; Henning P. Düsedau; Stefanie Ehrentraut; Olga Geisel; Oliver von Bohlen und Halbach; Peter Gass; Ildiko Rita Dunay; Rainer Hellweg

doi:10.1055/a-1363-1680

Pharmacopsychiatry, Table of Contents

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

Björn H. Schott

¹Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Germany

²Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany

³Leibniz Institute for Neurobiology, Department of Behavioral Neurology, Magdeburg, Germany

⁴German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany

,

Golo Kronenberg

²Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany

⁵University of Leicester and Leicestershire Partnership NHS Trust, Leicester, United Kingdom

,

Ulrike Schmidt

¹Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Germany

⁶Department of Psychiatry and Psychotherapy, University Medical Center Bonn, Bonn, Germany

,

Henning P. Düsedau

⁷Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany

,

Stefanie Ehrentraut

⁷Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany

,

Olga Geisel

²Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany

,

Oliver von Bohlen und Halbach

⁸Institute of Anatomy and Cell Biology, Universitätsmedizin Greifswald, Greifswald, Germany

,

Peter Gass

⁹Central Institute for Mental Health, Department of Psychiatry and Psychotherapy, Heidelberg University, Mannheim Faculty, Germany

,

Ildiko Rita Dunay‡

⁷Institute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, Germany

,

Rainer Hellweg‡

²Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany

› Author Affiliations

Abstract

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 (p75NTR^ExIII−/−) 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, p75NTR^ExIII−/− 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.

Key words

brain-derived neurotrophic factor - BDNF - interleukin 6 - IL-6 - p75NTR - stress - hippocampus

Full Text

References

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