Hormonal and synaptic influences of serotonin on adult neurogenesis (original) (raw)

The role of serotonin in adult hippocampal neurogenesis

Behavioural brain research, 2015

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 antidepres...

Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

Frontiers in cellular neuroscience, 2017

The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1) mice with altered central 5-HT levels from embryonic stages, (2) mice with deletion of 5-HT receptors from embryonic stages, and (3) mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal...

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry

eneuro, 2017

Significance Statement Alterations in brain serotonin (5-HT) levels during development can interfere with neuronal circuitry establishment and contribute to behavioral disturbances in adult life. It remains enigmatic whether wiring patterns can be reshaped by fluctuations of 5-HT content in the adult brain. In this study, we show for the first time that the adult serotonergic circuitry is susceptible to perturbations of serotonin homeostasis. These results provide evidence of lifelong requirement of proper 5-HT levels to preserve the serotonergic axonal wiring.

Lack of brain serotonin affects postnatal development and serotonergic neuronal circuitry formation

Molecular Psychiatry, 2012

Despite increasing evidence suggests that serotonin (5-HT) can influence neurogenesis, neuronal migration and circuitry formation, the precise role of 5-HT on central nervous system (CNS) development is only beginning to be elucidated. Moreover, how changes in serotonin homeostasis during critical developmental periods may have etiological relevance to human mental disorders, remains an unsolved question. In this study we address the consequences of 5-HT synthesis abrogation on CNS development using a knockin mouse line in which the tryptophan hydroxylase 2 (Tph2) gene is replaced by the eGFP reporter. We report that lack of brain 5-HT results in a dramatic reduction of body growth rate and in 60% lethality within the first 3 weeks after birth, with no gross anatomical changes in the brain. Thanks to the specific expression of the eGFP, we could highlight the serotonergic system independently of 5-HT immunoreactivity. We found that lack of central serotonin produces severe abnormalities in the serotonergic circuitry formation with a brain region-and time-specific effect. Indeed, we observed a striking reduction of serotonergic innervation to the suprachiasmatic and thalamic paraventricular nuclei, while a marked serotonergic hyperinnervation was found in the nucleus accumbens and hippocampus of Tph2HeGFP mutants. Finally, we demonstrated that BDNF expression is significantly up-regulated in the hippocampus of mice lacking brain 5-HT, mirroring the timing of the appearance of hyperinnervation and thus unmasking a possible regulatory feedback mechanism tuning the serotonergic neuronal circuitry formation. On the whole, these findings reveal that alterations of serotonin levels during CNS development affect the proper wiring of the brain that may produce long-lasting changes leading to neurodevelopmental disorders.

Role of Production and Degradation of Serotonin During Development

The Open Neuroscience Journal, 2009

Serotonin (5-hydroxytryptamine [5-HT]) is one of the major neurotransmitter in the brain. Since 5-HT is carried by 5-HT transporters and the biological activities of 5-HT are exerted through 5-HT receptors, disturbed regulation of 5-HT transporters and receptors in the adult brain has been implicated in pathological conditions in central nervous systems. On the other hand, proper 5-HT neurotransmission during development underlies the mature functional architecture of serotonergic neurons, and an increasing body of evidence suggests the involvement of developmental brain disturbances in psychiatric disorders. Genetic mouse models have shown that 5-HT receptors and the 5-HT transporter acting during developmental stages modulate developmental processes. In addition, recent works demonstrated that appropriate 5-HT production and 5-HT degradation during develoment are needed for the development of 5-HT neurons and brain functions in the adult. In this review article, we focus on the importance of activities of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis and monoamine oxidase A (MAOA), a catabolic enzyme responsible for degradation of 5-HT during development for the brain functions in the adult.

The developmental role of serotonin: news from mouse molecular genetics

Nature Reviews Neuroscience, 2003

There is increasing evidence that neurotransmitters are used as developmental signals, which modulate the construction and plasticity of brain circuits. Serotonin (5-hydroxytryptamine or 5-HT) was the first neurotransmitter for which a developmental role was suspected. Serotonergic neurons are among the earliest neurons to be generated, and 5-HT is released by growing axons before conventional synapses are established. Pharmacological studies initially showed that 5-HT can modulate a number of developmental events, including cell division, neuronal migration, cell differentiation and synaptogenesis 1-5 . It therefore came as a surprise that targeted deletions of 5-HT receptors or of genes involved in 5-HT metabolism in mice caused no gross abnormalities of brain development , or at least not the marked alterations that had been expected on the basis of the previous pharmacological analyses. One of the reasons for this discrepancy is that there is a large variety of 5-HT receptors, and that each receptor might have a limited set of actions during specific periods in development.

The maturation of cortical serotonin binding sites

Developmental Brain Research, 1981

Binding of serotonin to rat brain membranes increased linearly from birth to adulthood, but newborn receptor densities were already 39% of adult levels. These data suggest a postnatal development of serotonin receptors, coincident with synaptic maturation but do not preclude a nontransmitter function for serotonin during early maturation.

Serotonin drives striatal synaptic plasticity in a sex-related manner

Neurobiology of Disease, 2021

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Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals

Acta neurobiologiae experimentalis, 2004

It is well documented that in mammals new neurons are generated in the dentate gyrus (DG) and integrated into hippocampal circuits throughout their life. However, functions of these newly generated cells are still hotly debated. One of the important factors that may influence the rate of DG neurogenesis is serotonin. Apart from being a neurotransmitter and neuromodulator it plays many other roles in the central nervous system, including the role of a trophic factor influencing functional state of neurons. In this review I discuss the changing views on adult hippocampal neurogenesis then briefly describe the anatomy and function of the hippocampus, focusing on its serotonergic innervation and receptors. Further, the possible role of serotonin and the newly generated DG neurons in hippocampus-dependent memory is discussed. Finally mechanisms by which serotonin and its receptors influence neurogenesis in the adult DG are summarized and hypotheses linking the decreased rate of DG neurog...