神经损伤与修复
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Figure 1｜Region-specific effects of serotonergic signaling on adult neurogenesis.
The neuromodulatory transmitter serotonin (5-hydroxytryptamine, 5-HT) is synthesized by neurons located in the brainstem, which project more or less densely to the entire central nervous system (Charnay and Leger, 2010). Serotonin regulates a variety of physiological functions, including food intake, reward, reproduction, sleep-wake cycle, memory, cognition, emotion, and mood (Charnay and Leger, 2010). Consistently, dysfunctions of the serotonergic system are involved in the development or progression of mental disorders including autism, insomnia, anxiety, depression, schizophrenia, Parkinson’s disease, or Alzheimer’s disease (Charnay and Leger 2010). Many of these diseases (e.g., autism, schizophrenia, depression, Parkinson’s disease, Alzheimer’s disease) present with concomitant impairment of olfaction (and memory), often accompanied by a reduced volume of the olfactory bulb (OB; Figure 1A) and hippocampus. These functional impairments may result from distorted adult neurogenesis in the respective neurogenic niches, as OB and hippocampal dentate gyrus are the two major areas of the adult mammalian brain where adult-born cells are generated throughout life. A wide range of studies documents the involvement of adult-born cells in short- and long-term olfactory memory; perceptual, associative, and fear learning, etc. (summarized in Lepousez et al., 2015; Fomin-Thunemann et al., 2020).
Interestingly, adult neurogenesis and olfactory memory are positively modulated by fluoxetine, an antidepressant drug and selective serotonin reuptake inhibitor (Siopi et al., 2016). Cumulative evidence points towards a specific role for serotonin in adult neurogenesis, as it has been shown that serotonin modulates the fate and functional state of adult-born cells throughout the entire life. Serotonergic projections innervate both the hippocampus and OB (Charnay and Leger, 2010), as well as their respective neurogenic niches, the subgranular zone and subventricular zone (SVZ) (Soumier et al., 2010; Garcia-Gonzalez et al., 2017). Serotonergic fibers innervating the OB originate from the dorsal and medial raphe nuclei and primarily innervate the superficial glomerular layer of the OB (Figure 1B and C), with sparser innervation of granule and mitral cell layers (Petzold et al., 2009; Fletcher and Chen, 2010).