The 5-HT 1A Receptor

Serotonin 1A (5-HT ) receptors play a direct role in neuronal development, cell proliferation, and dendritic branching. We hypothesized that variability in 5-HT binding can affect cortical thickness, and may account for a subtype of major depressive disorder (MDD) in which both are altered. To evaluate this, we measured cortical thickness from structural magnetic resonance imaging (MRI) and 5-HT binding by positron emission tomography (PET) in an exploratory study. To examine a range of 5-HT binding and cortical thickness values, we recruited 25 healthy controls and 19 patients with MDD. We hypothesized increased 5-HT binding in the raphe nucleus (RN) would be negatively associated with cortical thickness due to reduced serotonergic transmission. Contrary to our hypothesis, raphe 5-HT binding was positively correlated with cortical thickness in right posterior cingulate cortex (PCC), a region implicated in the default mode network. Cortical thickness was also positively correlated with 5-HT in each cortical region. We further hypothesized that the strength of 5-HT -cortical thickness correlation depends on the number of axons between the raphe nucleus and each region. To explore this we related 5-HT -cortical thickness correlation coefficients to the number of tracts connecting that region and the raphe, as measured by diffusion tensor imaging (DTI) in an independent sample. The 5-HT -cortical thickness association correlated significantly with the number of tracts to each region, supporting our hypothesis. We posit a defect in the raphe may affect the PCC within the default mode network in MDD through serotonergic fibers, resulting in increased ruminative processing.

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Relations between cortical thickness, serotonin 1A receptor binding, and structural connectivity: A multimodal imaging study

Pillai

Malhotra

Rupert

et al. 2017

Human Brain Mapping

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5‐HT 1A and 2A receptor positive cells in the cerebella of mice and human and their decline during aging

Yew

Yeung

Wai

et al. 2009

Microscopy Res & Technique

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This study evaluated the 5-HT1A and 5-HT2A receptor positive cells in the cerebella of mice and human by immunocytochemistry. Mice were of ages 1, 3, and 12 months whereas the human subjects were divided into two groups, a younger 57-78 years old group and an older 82-91 years old group. Both 5-HT1A and 5-HT2A receptor positive cells were observed in the molecular and granular layers of the cerebella of mice and human. Although there was a decline in these positive cells during aging, no regional difference in the positive cells were observed in the anterior, middle, and posterior regions of the cerebella.

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Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals

Yeung

Kung

Yew

2010

AGE

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Serotonin receptor 1A and 2A positive cells in postmortem brainstems were demonstrated via immunohistochemistry in eight control age-matched elderly individuals and eight Alzheimer patients. The 5-HT1A positive cells were found in substantia nigra, pontile nucleus, and vagal as well as dorsal raphe nucleus, while 5-HT2A receptor positive cells were found in motor, sensory and spinal trigeminal nuclei, pontile nucleus, substantia nigra, and nucleus solitarius. A comparison in density of positive cells per unit area was made between control age-matched and Alzheimer individuals. Statistically significant differences (p ≤ 0.01) in density were observed in 5-HT1A cells in pontile, dorsal raphe, and vagal nuclei between control age-matched and Alzheimer, and in 5-HT2A positive cells in the sensory trigeminal nucleus, between control and Alzheimer. This de novo study indicated the presence of 5-HT1A and 5-HT2A receptor positive cells in the above nuclei of human brainstem and revealed differences in density between control age-matched and Alzheimer, indicating possible functional derangements in Alzheimer patients in these areas. In addition, colocalization studies indicated that 5-HT1A receptors were in cholinergic cells and gamma-aminobutyric acid positive fibers were linked to 5-HT2A receptor positive cells. It is hoped that understanding these two important 5-HT receptors and their localization might lead to advances in future therapeutic development.

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The 5-HT 1A Receptor

Cited by 9 publications

References 93 publications

Relations between cortical thickness, serotonin 1A receptor binding, and structural connectivity: A multimodal imaging study

Relations between cortical thickness, serotonin 1A receptor binding, and structural connectivity: A multimodal imaging study

5‐HT 1A and 2A receptor positive cells in the cerebella of mice and human and their decline during aging

Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals

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