Differentiated HT22 cells as a novel model for in vitro screening of serotonin reuptake inhibitors
The mouse hippocampal neuronal cell line HT22 is frequently used as an model to investigate the role of hippocampal cholinergic neurons in cognitive functions. HT22 cells are derived from hippocampal neuronal HT4 cells. However, whether these cells exhibit the serotonergic neuronal phenotype observe...
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Published in | Frontiers in pharmacology Vol. 13; p. 1062650 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
10.01.2023
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Subjects | |
Online Access | Get full text |
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Summary: | The mouse hippocampal neuronal cell line HT22 is frequently used as an
model to investigate the role of hippocampal cholinergic neurons in cognitive functions. HT22 cells are derived from hippocampal neuronal HT4 cells. However, whether these cells exhibit the serotonergic neuronal phenotype observed in mature hippocampal neurons has not been determined yet. In this present study, we examined whether the differentiation of HT22 cells enhances the serotonergic neuronal phenotype, and if so, whether it can be used for antidepressant screening. Our results show that differentiation of HT22 cells promoted neurite outgrowth and upregulation of N-methyl-D-aspartate receptor and choline acetyltransferase, which is similar to that observed in primary cultured hippocampal neurons. Furthermore, proteins required for serotonergic neurotransmission, such as tryptophan hydroxylase 2, serotonin (5-hydroxytryptamine, 5-HT)
receptor, and serotonin transporter (SERT), were significantly upregulated in differentiated HT22 cells. The transcription factor Pet-1 was upregulated during HT22 differentiation and was responsible for the regulation of the serotonergic neuronal phenotype. Differentiation also enhanced the functional serotonergic properties of HT22 cells, as evidenced by increase in intracellular 5-HT levels, serotonin transporter SERT glycosylation, and 5-HT reuptake activity. The sensitivity of 5-HT reuptake inhibition by venlafaxine in differentiated HT22 cells (IC
27.21 nM) was comparable to that in HEK293 cells overexpressing serotonin transporter SERT (IC
30.65 nM). These findings suggest that the differentiation of HT22 cells enhances their functional serotonergic properties, and these cells could be a potential
system for assessing the efficacy of antidepressant 5-HT reuptake inhibitors. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Agnieszka Zelek-Molik, Polish Academy of Sciences, Poland Edited by: Philippe De Deurwaerdere, Université de Bordeaux, France Reviewed by: Wieslawa Agnieszka Fogel, Polish Academy of Sciences, Poland This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2022.1062650 |