Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin

Diaz, Silvina Laura; Narboux-Nême, Nicolas; Trowbridge, Sara; Scotto-Lomassese, Sophie; Borgmann, Felix Bruno Kleine; Jessberger, Sebastian; Giros, Bruno; Maroteaux, Luc; Deneris, Evan S.; Gaspar, Patricia

doi:10.1111/ejn.12297

Cited by 38 publications

(76 citation statements)

References 45 publications

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“…For 5-HT2A receptors, labeling revealed a dense staining in the hilus, whereas 5-HT2B (Diaz et al, 2013) and 5-HT2C receptors mostly mark adult granule cells (Klempin et al, 2010). 5-HT3 receptor mRNA expression was seen in hilar interneurons (Tecott et al, 1993) that was confirmed by in situ hybridization (Diaz et al, 2013). We hypothesize that the distinct actions of receptor subtypes could mediate the homeostasis of serotonin signaling in the 5 hippocampus.…”

Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 60%

“…Their expression pattern varies with 5-HT1A receptor immunoreactivity found on type-1 to type-2b cells in the SGZ as well as on interneurons. For 5-HT2A receptors, labeling revealed a dense staining in the hilus, whereas 5-HT2B (Diaz et al, 2013) and 5-HT2C receptors mostly mark adult granule cells (Klempin et al, 2010). 5-HT3 receptor mRNA expression was seen in hilar interneurons (Tecott et al, 1993) that was confirmed by in situ hybridization (Diaz et al, 2013).…”

Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 68%

“…Serotonin depletion also leads to a decrease in 4 dendritic spine density of granule cells (Yan et al, 1997). However, controversial data exist showing that PCPA treatment, but not the neurotoxin 5,7-DHT (Huang and Herbert, 2005b) might decrease the number of precursor cells at 1 day and 4 weeks later (Jha et al, 2006), while chronic PCPA treatment also leads to increased survival of precursor cells in the DG of wild type animals mimicking models with serotonin deficiency (Diaz et al, 2013). On balance, data from these studies reveal that serotonin depletion or a decline in serotonin synthesis has long-term regulatory effects on adult hippocampal neurogenesis, however with noticeable contradictive effects.…”

Section: The Effect Of Pharmacological Serotonin Depletion or Enhancementioning

confidence: 99%

“…Serotonergic targets within the DG express a variety of 5-HT receptors that in turn dictate the response from efferent activity (Brezun and Daszuta, 2000, Klempin et al, 2010, Diaz et al, 2013. Their expression pattern varies with 5-HT1A receptor immunoreactivity found on type-1 to type-2b cells in the SGZ as well as on interneurons.…”

Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 99%

“…Elucidation of adult hippocampal neurogenesis revealed no measurable changes in baseline proliferation of precursor cells in mice that are almost devoid of brain serotonin (Tph2 -/-, VMAT2 SERT-Cre ) or with a drastic reduction in serotonin levels (Tph2KI, Pet1 -/-) (Diaz et al, 2013, Klempin et al, 2013, Sachs et al, 2013. Considering the results reviewed above on pharmacological depletion of serotonin signaling that leads to a decrease in neurogenesis, it is surprising that sustained neurogenesis can occur in the absence of serotonin.…”

Section: Animal Models: Addressing the Controversy Of Serotonin's Rolmentioning

confidence: 99%

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The role of serotonin in adult hippocampal neurogenesis

Alenina

Klempin

2015

Behavioural Brain Research

163

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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.

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Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 60%

Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 68%

Section: The Effect Of Pharmacological Serotonin Depletion or Enhancementioning

confidence: 99%

Section: Pharmacological 5-ht Receptor Targeting Studies and Baselinementioning

confidence: 99%

Section: Animal Models: Addressing the Controversy Of Serotonin's Rolmentioning

confidence: 99%

See 3 more Smart Citations

The role of serotonin in adult hippocampal neurogenesis

Alenina

Klempin

2015

Behavioural Brain Research

163

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Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability

et al. 2014

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Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain–limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy—focal granule cell bilamination in the dentate, a variant of granule cell dispersion—is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner’s office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2 % (47/114) of the unexplained group compared to 7.7 % (3/39) of the explained (control) group (p < 0.001). It was associated with a cluster of other dentate developmental abnormalities that reflect defective neuronal proliferation, migration, and/or survival. Dentate lesions in a large subset of infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-014-1357-0) contains supplementary material, which is available to authorized users.

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Ascending serotonin neuron diversity under two umbrellas

Commons

2016

Brain Struct Funct

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Forebrain serotonin relevant for many psychological disorders arises in the hindbrain, primarily within the dorsal and median raphe nuclei (DR and MR). These nuclei are heterogeneous, containing several distinct groups of serotonin neurons. Here, new insight into the afferent and efferent connectivity of these areas is reviewed in correlation with their developmental origin. These data suggest that the caudal third of the DR, the area originally designated B6, may be misidentified as part of the DR as it shares many features of connectivity with the MR. By considering the rostral DR independently and affiliating the B6 to the MR, the diverse subgroups of serotonin neurons can be arranged with more coherence into two umbrella groups, each with distinctive domains of influence. Serotonin neurons within the rostral DR are uniquely interconnected with brain areas associated with emotion and motivation such as the amygdala, accumbens and ventral pallidum. In contrast serotonin neurons in the B6 and MR are characterized by their dominion over the septum and hippocampus. This distinction between the DR and B6/MR parallels their developmental origin and likely impacts their role in both behavior and psychopathology. Implications and further subdivisions within these areas are discussed.

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Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin

Cited by 38 publications

References 45 publications

The role of serotonin in adult hippocampal neurogenesis

The role of serotonin in adult hippocampal neurogenesis

Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability

Ascending serotonin neuron diversity under two umbrellas

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