Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats

doi:10.1016/S0306-4522(98)00693-9

Neuroscience

Volume 89, Issue 4, April 1999, Pages 999-1002

https://doi.org/10.1016/S0306-4522(98)00693-9 Get rights and content

Abstract

During adulthood, neuronal precursor cells persist in two discrete regions, the subventricular zone[19]and the hippocampal subgranular zone,[11]as recently demonstrated in primates.[10]To date, a few factors such as adrenal steroids[9]and trophic factors[13]are known to regulate adult neurogenesis. Since neuronal activity may also influence cellular development and plasticity in brain, we investigated the effects of serotonin depletion on cell proliferation occurring in these regions. Indeed, in addition to its role as a neurotransmitter, 5-hydroxytryptamine (serotonin) is considered as a developmental regulatory signal.14, 22Prenatal depletion in 5-hydroxytryptamine delays the onset of neurogenesis in 5-hydroxytryptamine target regions[14]and 5-hydroxytryptamine promotes the differentiation of cortical and hippocampal neurons.15, 23Although in the adult brain, a few studies have suggested that 5-hydroxytryptamine may play a role in neuronal plasticity by maintaining the synaptic connections in the cortex and hippocampus,3, 6, 16no information is actually available concerning the influence of 5-hydroxytryptamine on adult neurogenesis. If further work confirms that new neurons can be produced in the adult human brain as is the case for a variety of species, it is particularly relevant to determine the influence of 5-hydroxytryptamine on neurogenesis in the hippocampal formation, a part of the brain largely implicated in learning and memory processes. Indeed, lack of 5-hydroxytryptamine in the hippocampus has been associated with cognitive disorders, such as depression,[1]schizophrenia and Alzheimer's disease.[7]

In the present study, we demonstrated that both inhibition of 5-hydroxytryptamine synthesis and selective lesions of 5-hydroxytryptamine neurons are associated with decreases in the number of newly generated cells in the dentate gyrus, as well as in the subventricular zone.

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Acknowledgements

The authors wish to thank Dr. G. Rougon for generous gift of PSA-N-CAM antibody.

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Distribution of 5HT receptors during the regeneration process after spinal cord transection in goldfish
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Spinal cord injury in teleosts leads to a fibrous scar, but axons sometimes spontaneously regenerate beyond the scar. In goldfish, regenerating axons enter the scar through tubular structures and enlargement of the tubular diameter is proportional to the increase in the number of regenerating axons. During the regeneration process, mast cells containing 5-hydroxytryptamine (5HT) are recruited to the injury site, and 5HT neurons are newly generated. Here, we investigated the distribution of 5HT receptors during this process to determine their role in remodeling the fibrous scar and tubular structures. At 2 weeks after spinal cord transection (SCT) in goldfish, expression of the 5HT2A and 5HT2C receptor subtypes was observed in the ependymo-radial glial cells lining the central canal of the spinal cord. 5HT2A was expressed at the luminal surface, suggesting that it is receptive to 5HT in the cerebrospinal fluid. 5HT2C, on the other hand, was expressed around the nuclei and in the radial processes protruding from the basal surface, suggesting that it is receptive to 5HT released from nearby nerve endings. 5HT2C was also expressed in the fibrous scar where mast cells containing 5HT were abundant. 5HT1B expression was coincident with the basement membrane bordering the fibrous scar and the surrounding nervous tissue, and with the basement membrane of the tubular structure through which axons pass during regeneration. Our findings suggest that multiple 5HT receptors are involved in remodeling the injured site during the regenerative process following SCT. Ependymo-radial glial cells expressing 5HT2A and 5HT2C are involved in neurogenesis and gliogenesis, which might contribute to remodeling the fibrous scar in coordination with 5HT-containing mast cells. Coincident expression of 5HT1B with the basement membrane might be involved in remodeling the tubular structures, thereby promoting axonal regeneration.
Cortical regulation of neurogenesis and cell proliferation in the ventral subventricular zone
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Neurogenesis and differentiation of neural stem cells (NSCs) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. In this study, we identify a circuit that regulates neurogenesis and cell proliferation in the lateral ventricle-subventricular zone (LV-SVZ). Our results demonstrate that direct glutamatergic projections from the anterior cingulate cortex (ACC), as well as inhibitory projections from calretinin⁺ local interneurons, modulate the activity of cholinergic neurons in the subependymal zone (subep-ChAT⁺). Furthermore, in vivo optogenetic stimulation and inhibition of the ACC-subep-ChAT⁺ circuit are sufficient to control neurogenesis in the ventral SVZ. Both subep-ChAT⁺ and local calretinin⁺ neurons play critical roles in regulating ventral SVZ neurogenesis and LV-SVZ cell proliferation.
Adult Neurogenesis in the Mammalian Hypothalamus: Impact of Newly Generated Neurons on Hypothalamic Function
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In mammals, adult neurogenesis was first demonstrated in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus of the hippocampal formation. Further research showed that adult neurogenesis persists in other brain structures, such as the cerebral cortex, piriform cortex, striatum, amygdala, and hypothalamus. However, the origin of newly generated cells in these structures is not clear. Accumulating evidence indicates that newly generated neurons in the striatum or amygdala are derived from the SVZ, while in the adult hypothalamus, the proliferation of progenitor cells occurs in the ependymal cells lining the third ventricle, which give rise to new neurons. The heterogeneous cellular organization of the ependymal layer of the hypothalamus leads to different conclusions regarding the type of hypothalamic progenitor cells. In addition, adult hypothalamic neurogenesis occurs at low levels. Based on comparative and functional approaches, we synthesize the knowledge of newly generated cells in the adult hypothalamus. The aim of this review is to provide new insights on adult neurogenesis in the mammalian hypothalamus, with particular attention given to marsupial species. We highlight the number of adult-born neurons in various hypothalamic nuclei, debating whether their low number has an impact on hypothalamic function.
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Various brain regions/nuclei project axons to the subventricular zone (SVZ), a postnatal neurogenic niche. In adults, neurogenesis is controlled by neuronal activity, via neurotransmitters. Glutamate is a major excitatory neurotransmitter, and glutamate receptors are expressed in SVZ cells. Although the cerebral cortex is a major source of glutamate and the medial cortex projects axons to the medial striatum next to the SVZ, it remains unclear whether cortical neurons regulate adult neurogenesis in vivo. First, to analyze axonal projection, plasmid vector expressing DsRed was introduced to the medial cortex by in utero electroporation. At the adult stage, DsRed-labeled axons were detected in the dorsolateral, striatal, and septal areas of the SVZ, and where they were in contact with neuroblasts. Furthermore, maturation of the cortical projection and the SVZ appeared to synchronize during postnatal stages. Next, stab injuries were made in the bilateral medial cortex to interrupt cortical input to the SVZ. At 17 days post-injury, cell proliferation in the SVZ and tangential migration of neuroblasts to the olfactory bulb were not significantly affected. There were clusters of neuroblasts in the striatum close to the SVZ in all experimental groups, but the number and size of neuroblast clusters were significantly larger in the medial cortex-injured group compared with the other experimental groups. These neuroblast clusters had a morphology of tangentially migrating cells to the olfactory bulb. These results suggest that cortical input to the SVZ inhibits the radial migration of neuroblasts to converge with the migration pathway in vivo.
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Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.
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Letter to NeuroscienceDepletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats

Abstract

Section snippets

Acknowledgements

Brain Res.

Neuroscience

Neurosci. Res.

Brain Res.

Devl Brain Res.

The role of serotonin in the pathophysiology and treatment of schizophrenia

J. Neuropsychiat.

Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains

Proc. natn. Acad. Sci. U.S.A.

Serotonin in Alzheimer-type dementia and other dementing illness

Ann. N. Y. Acad. Sci.

Modulation of cell adhesion during induction, histogenesis and perinatal development of the nervous system

A. Rev. Neurosci.

Adrenal hormones suppress cell division in the adult rat dentate gyrus

J. Neurosci.

Letter to Neuroscience
Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats