Utility of organotypic raphe slice cultures to investigate the effects of sustained exposure to selective 5‐HT reuptake inhibitors on 5‐HT release

Nagayasu, Kazuki; Yatani, Yumi; Kitaichi, Maiko; Kitagawa, Yutaka; Shirakawa, Hisashi; Nakagawa, Takayuki; Kaneko, Shuji

doi:10.1111/j.1476-5381.2010.00978.x

Cited by 15 publications

(24 citation statements)

References 74 publications

(94 reference statements)

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“…2D). We previously reported that sustained treatment with SSRIs dramatically enhanced exocytotic 5-HT release in the raphe slice cultures [13]. Here, we examined whether TSA treatment further augments the enhanced 5-HT release in response to sustained treatment with an SSRI, citalopram.…”

Section: Tsa Treatment Increased 5-ht Release From Organotypic Raphe mentioning

confidence: 96%

“…Tissue contents and extracellular levels of 5-HT were measured as previously described [13]. Briefly, for measurement of tissue contents of 5-HT, the brain slices were homogenized and centrifuged, and the supernatants were analyzed by high performance liquid chromatography with an electrochemical detector (HPLC-ECD) (Eicom, Kyoto, Japan).…”

Section: Measurement Of Tissue Contents and Extracellular Levels Of 5-htmentioning

confidence: 99%

“…Rat raphe slice cultures were prepared as previously described [12,13]. Briefly, coronal sections (350 m thick) containing the dorsal and median raphe nuclei were prepared from Wistar/ST rat pups, and maintained in culture for 14-16 days.…”

Section: Preparation Of Rat Organotypic Raphe Slice Culturesmentioning

confidence: 99%

“…Western blot analysis for TPH was performed as previously described [12,13]. Briefly, proteins extracted from slices were subjected to SDS-PAGE.…”

Section: Western Blotmentioning

confidence: 99%

“…We previously reported that organotypic raphe slice cultures that possess functional 5-HT neurons and local neuronal circuits provide a useful tool for investigation of the effects of antidepressants on the 5-HT system [12,13]. In this study, we examined whether a pan-HDAC inhibitor, trichostatin A (TSA), affects 5-HT neuronal function using organotypic raphe slice cultures.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures

Asaoka

Nagayasu

Nishitani

et al. 2015

Neuroscience Letters

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Inhibition of histone deacetylases (HDACs) is a promising approach for the treatment of mood disorders. However, the effects of HDAC inhibition on the serotonin (5-HT) system, a common target for psychiatric disorders, are poorly understood. Here, we show that a broad-spectrum HDAC inhibitor, trichostatin A (TSA), enhances the function of 5-HT neurons in organotypic raphe slice cultures. Sustained treatment with TSA (1μM) for 2 or 4 days significantly increased the 5-HT tissue content and tryptophan hydroxylase 2 (TPH2) expression, which were accompanied by hyper-acetylation of histone H3 in the promoter region of the TPH2 gene. TSA treatment for 4 days increased the extracellular 5-HT level, which was significantly suppressed in the presence of the selective AMPA receptor (AMPAR) antagonist NBQX. Moreover, the expression of both the AMPAR subunit GluA2 and Ca(2+)/calmodulin-dependent kinase II α (CaMKIIα) mRNAs were significantly increased by TSA treatment. Co-treatment with the CaMKII inhibitors KN-62 and KN-93 prevented the TSA-induced increase in 5-HT release, but had no effect on the increases in 5-HT tissue content. These results suggest that inhibition of HDACs increases 5-HT synthesis and release by epigenetic mechanisms, and that 5-HT release is mediated by the enhancement of AMPAR-mediated excitatory inputs and CaMKII signaling.

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Section: Tsa Treatment Increased 5-ht Release From Organotypic Raphe mentioning

confidence: 96%

Section: Measurement Of Tissue Contents and Extracellular Levels Of 5-htmentioning

confidence: 99%

Section: Preparation Of Rat Organotypic Raphe Slice Culturesmentioning

confidence: 99%

“…Western blot analysis for TPH was performed as previously described [12,13]. Briefly, proteins extracted from slices were subjected to SDS-PAGE.…”

Section: Western Blotmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures

Asaoka

Nagayasu

Nishitani

et al. 2015

Neuroscience Letters

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Postnatal exposure to fluoxetine led to cognitive‐emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats

Meurer

Linhares

Lima

et al. 2021

Intl J of Devlp Neuroscience

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The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (~PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7‐PND21)‐ or vehicle‐treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety‐ and depression‐like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short‐term (but not long‐term) recognition memory impairments, and reduced parvalbumin‐positive interneurons in the hippocampus. In addition, the results revealed developmental sex‐dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.

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Dorsal raphe serotonergic neurons preferentially reactivate dorsal dentate gyrus cell ensembles associated with positive experience

et al. 2023

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Utility of organotypic raphe slice cultures to investigate the effects of sustained exposure to selective 5‐HT reuptake inhibitors on 5‐HT release

Cited by 15 publications

References 74 publications

Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures

Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures

Postnatal exposure to fluoxetine led to cognitive‐emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats

Dorsal raphe serotonergic neurons preferentially reactivate dorsal dentate gyrus cell ensembles associated with positive experience

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