TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment

By Yun Li, Bryan W. Luikart, S. Birnbaum, Jing Chen, C. Kwon, S. Kernie, R. Bassel-Duby, L. Parada. Neuron, 2008

636 citations recorded by the source corpus.

Summary Adult hippocampal neurogenesis is stimulated by chronic administration of antidepressants (ADs) and by voluntary exercise. Neural progenitor cells in the dentate gyrus (DG) that are capable of continuous proliferation and neuronal differentiation are the source of such structural plasticity. Here we report that mice lacking the receptor tyrosine kinase TrkB in hippocampal NPCs have impaired proliferation and neurogenesis. When exposed to chronic AD or wheel running, no increase in proliferation or neurogenesis is observed. Ablation of TrkB also renders these mice behaviorally insensitive to antidepressive treatment in depression and anxiety-like paradigms. In contrast, mice lacking TrkB only in differentiated DG neurons display typical neurogenesis and respond normally to chronic AD. Thus, our data establish an essential cell autonomous role for TrkB in regulating hippocampal neurogenesis, behavioral sensitivity to antidepressive treatments, and support the notion that impairment of the neurogenic niche is an etiological factor for refractory responses to antidepressive regimen.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/e97ced56437a2aa285dc712610321d85de2a207e

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Citations in the corpus

Modification of hippocampal circuitry by adult neurogenesis (2012, background): “In contrast, deleting TrkB in differentiated neurons of the same brain regions does not affect neurogenesis or the behavioral responses to antidepressants, supporting the notion that dentate NSCs are a required component in the amelioration of depression (Li et al., 2008).”
Exercise training increases size of hippocampus and improves memory (2011, background): “Exercise increases levels of BDNF in the hippocampus (5, 7, 20), which, along with the trkB receptor, is considered to be a partial mediator of the enhancing effect of exercise on learning and memory (7, 8).”
Exercise and the brain: something to chew on (2009, background): “However, it should be noted that exercise has acute and robust neurogenic effects, whereas fluoxetine requires chronic administration and has variable effects on cell genesis [93-95].”
Immune modulation of learning, memory, neural plasticity and neurogenesis. (2011, neutral): “As described above (Section 1.4.3.3), BDNF has been implicated in hippocampal-dependent memory (Barnes and Thomas, 2008; Heldt et al., 2007), LTP (Lu et al., 2008) and neurogenesis (Li et al., 2008).”
Linking Molecules to Mood: New Insight Into the Biology of Depression (2010, neutral): “This practice, stemming from the “neurotrophic hypothesis” of depression (65), is based on three main observations: an impairment of hippocampal BDNF signaling produces certain depression-related behaviors and impairs the actions of antidepressants (66-68), experimental increases in hippocampal BDNF”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”
Epigenetic regulation of neurogenesis in the adult mammalian brain (2011, background): “One of the best known targets of MeCP2 is brain-derived neurotrophic factor (BDNF), which has been implicated in regulating several aspects of adult hippocampal neurogenesis, including proliferation of neural progenitors (Li et al., 2008b) and development of newborn neurons (Schmidt & Duman, 2007).”
The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review (2016, background): “One study in rodents strongly supports the hypothesis that IGF-1 is involved in acute exercise-induced increases in hippocampal functioning [184].”
DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212 (2009, neutral): “…of the existing neuronal circuitry, including brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF), and neuregulins (NRGs) (Ghashghaei et al., 2006; Jin et al., 2002; Li et al., 2008; Ma et al., 2009; Schmidt and Duman, 2007).”
Experience dictates stem cell fate in the adult hippocampus. (2011, neutral): “Some indelible lineage studies have been carried out looking at the adult hippocampus (Ahn and Joyner, 2005; Imayoshi et al., 2008; Lagace et al., 2007; Li et al., 2008).”
The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity (2010, background): “…the hippocampal dentate gyrus (Madsen et al., 2000; Malberg et al., 2000; Warner-Schmidt and Duman, 2006) and in some cases, neurogenesis appears to be important for the behavioral effects of antidepressant drugs (Santarelli et al., 2003; Bergami et al., 2008; Li et al., 2008; David et al., 2009).”