Depletion of TrkB Receptors From Adult Serotonergic Neurons Increases Brain Serotonin Levels, Enhances Energy Metabolism and Impairs Learning and Memory

Madhusmita P Sahu; Yago Pazos-Boubeta; Anna Steinzeig; Katja Kaurinkoski; Michela Palmisano; Olgierd Borowecki; Timo Petteri Piepponen; Eero Castrén

doi:10.3389/fnmol.2021.616178

Depletion of TrkB Receptors From Adult Serotonergic Neurons Increases Brain Serotonin Levels, Enhances Energy Metabolism and Impairs Learning and Memory

Front Mol Neurosci. 2021 Apr 15:14:616178. doi: 10.3389/fnmol.2021.616178. eCollection 2021.

Authors

Madhusmita P Sahu¹, Yago Pazos-Boubeta¹, Anna Steinzeig¹, Katja Kaurinkoski¹, Michela Palmisano¹, Olgierd Borowecki^{1

2}, Timo Petteri Piepponen³, Eero Castrén¹

Affiliations

¹ Neuroscience Center, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland.
² Faculty of Philosopy and Social Sciences, Nicolaus Copernicus University in Toruń, Toruń, Poland.
³ Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.

Abstract

Neurotrophin brain-derived neurotrophic factor (BDNF) and neurotransmitter serotonin (5-HT) regulate each other and have been implicated in several neuronal mechanisms, including neuroplasticity. We have investigated the effects of BDNF on serotonergic neurons by deleting BDNF receptor TrkB from serotonergic neurons in the adult brain. The transgenic mice show increased 5-HT and Tph2 levels with abnormal behavioral phenotype. In spite of increased food intake, the transgenic mice are significantly leaner than their wildtype littermates, which may be due to increased metabolic activity. Consistent with increased 5-HT, the proliferation of hippocampal progenitors is significantly increased, however, long-term survival of newborn cells is unchanged. Our data indicates that BDNF-TrkB signaling regulates the functional phenotype of 5-HT neurons with long-term behavioral consequences.

Keywords: BDNF; TrkB; neuronal plasticity; neurotrophic factor; serotonin.