Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

Abstract

The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 -/-) mice lacking brain serotonin and serotonin transporter (SERT) deficient (SERT -/-) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 -/-mice, whereas no significant changes were observed in SERT -/-mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 -/-but not of SERT -/-mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression.

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

“…In stressrelated disorders depletion of serotonin reduces brain BDNF levels (Chen et al, 2007;Yoshida et al, 2012;Zhou et al, 2008). On the contrary, hypo-serotonergic mouse (Tph2-/-or Pet1-/-) showed increased BDNF levels in hippocampus and prefrontal cortex (Diaz et al, 2013;Klempin et al, 2013;Kronenberg et al, 2016;Sachs et al, 2013) and humans with serotonin transporter deficiency (hyperserotonin) reduced the availability of BDNF (Molteni et al, 2010), which enhances NSCs proliferation and neurogenesis (Arsenijevic and Weiss, 1998;Numakawa et al, 2017). Our findings support the negative role of serotonin on BDNF signaling and NSC plasticity.…”

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

“…In stress-related disorders, depletion of serotonin reduces brain BDNF levels [63][64][65]. On the contrary, hyposerotonergic mouse (Tph2−/− or Pet1−/−) showed increased BDNF levels in the hippocampus and prefrontal cortex [60][61][62]66], and humans with SERT deficiency (hyperserotonin) reduced the availability of BDNF [67], which enhances NSCs proliferation and neurogenesis [68,69]. Our findings support the negative role of serotonin on BDNF signaling and NSC plasticity.…”

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry

“…To investigate whether the increased density of serotonergic fibers in the hippocampus could be linked to an increase in the hippocampal brain-derived neurotrophic factor (BDNF) regulation that is known to be influenced by serotonin signaling (Hill et al, 2011; Migliarini et al, 2013; Homberg et al, 2014; Kronenberg et al, 2016), we analyzed BDNF mRNA expression levels performing ISH using 35 S-radiolabeled antisense BDNF probe on brain coronal sections of both TM- and vehicle-treated Tph2 GFP/fl ° x ::CMVCreER T mice at D30. Densitometric analysis of autoradiographic signal revealed that serotonin depletion did not impact BDNF mRNA transcriptional regulation (Fig.…”

“…As BDNF expression has been reported to be influenced by serotonin signaling (Hill et al, 2011; Migliarini et al, 2013; Homberg et al, 2014; Kronenberg et al, 2016), we wondered whether this neurotrophin could act as a potential molecular mediator in the establishment of the observed alterations in 5-HT fiber density. However, we failed to detect any significant alteration in the hippocampal level of BDNF in our Tph2 cKO mice, suggesting that other factors are likely involved in the response of 5-HT depletion during adult stages of life.…”