The role of serotonin in adult hippocampal neurogenesis

Abstract

Serotonin is probably best known for its role in conveying a sense of contentedness and happiness. It is one of the most unique and pharmacologically complex monoamines in both the peripheral and central nervous system (CNS). Serotonin has become in focus of interest for the treatment of depression with multiple serotonin-mimetic and modulators of adult neurogenesis used clinically. Here we will take a broad view of serotonin from development to its physiological role as a neurotransmitter and its contribution to homeostasis of the adult rodent hippocampus. This chapter reflects the most significant findings on cellular and molecular mechanisms from neuroscientists in the field over the last two decades. We illustrate the action of serotonin by highlighting basic receptor targeting studies, and how receptors impact brain function. We give an overview of recent genetically modified mouse models that differ in serotonin availability and focus on the role of the monoamine in antidepressant response. We conclude with a synthesis of the most recent data surrounding the role of serotonin in activity and hippocampal neurogenesis.This synopsis sheds light on the mechanisms and potential therapeutic model by which serotonin plays a critical role in the maintenance of mood.

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

“…Neurogenesis which has been shown to be involved in cognitive impairment and depression in humans and in a variety of rodent models, is a function of serotonergic regulation and may affect the response to antidepressants in both cognitive and affective behavioral domains (Adeosun et al, 2014;Alenina and Klempin, 2015;Anacker, 2014;Biscaro et al, 2012;Braun and Jessberger, 2014;Chadwick et al, 2011;Cho et al, 2015;Dimitrov et al, 2014;Gundersen et al, 2013;Hill et al, 2015;Jiang et al, 2015;Lin and Wang, 2014;Mendez-David et al, 2013;Morais et al, 2014;O'Leary and Cryan, 2014;Parihar et al, 2013;Pereira Dias et al, 2014;Ransome et al, 2012;Rotheneichner et al, 2014;Schoenfeld and Cameron, 2015;Seib et al, 2013;Serafini et al, 2014;Shetty, 2014;Suarez-Pereira et al, 2015;Yau et al, 2014). In young adult mice, antidepressants increase stem cell proliferation (Hodes et al, 2010;Santarelli et al, 2003;Tanti et al, 2013).…”

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

“…It might therefore be speculated that impaired serotonergic signaling is also accompanied by reduced neurogenesis. However, we and others have recently shown that in adult mice modified for no (Tph2 -/-, VMAT2 SERT-Cre ) or reduced brain serotonin (Tph2KI, Pet1 -/-) baseline levels of cell proliferation in the dentate gyrus are unexpectedly normal (reviewed in [19]). We speculate that sustained cell proliferation under conditions of serotonin deficiency most probably is the result of developmental compensation by other factors in the niche, e.g., BDNF.…”

Hippocampal Gene Expression Is Highly Responsive to Estradiol Replacement in Middle-Aged Female Rats

“…Serotonin regulates neuronal network excitability and modulates adult neurogenesis in the hippocampus (118). Granule cells and interneurons in the dentate gyrus receive serotonergic input from the brain stem (119). HT 2C is one of the receptor subtypes which mediates the effect of serotonin on neurogenesis (119).…”