Abstract
Repressor element-1 silencing transcription factor (REST) is highly expressed in the dorsal raphe where serotonin (5-hydroxytryptamine, 5-HT) neurons are located. REST works as a transcription factor for the 5-HT receptor and tryptophan hydroxylase two-gene expression. We hypothesized that REST is co-expressed in 5-HT neurons, which, if demonstrated, would be useful to understand the mechanism of 5-HT dysfunction-related disorders such as negative emotions and depression. Therefore, the present study was designed to examine the expression of the REST gene in the brain (forebrain, midbrain, and hindbrain) of adult male Nile tilapia (Oreochromis niloticus) using rt-PCR. Besides, using immunocytochemistry, co-localization of the REST gene was examined in 5-HT neurons and with neuronal-/glial-cell markers. We found a high expression of the REST gene in the midbrain region of the dorsal raphe, an area of 5-HT neurons. Double-label immunocytochemistry showed neuron-specific expression of REST co-localized in 5-HT neurons in the dorsal and ventral parts of the periventricular pretectal nucleus, paraventricular organ, and dorsal and medial raphe nucleus. Since midbrain 5-HT neurons express REST, we speculate that REST may control 5-HT neuronal activity related to negative emotions, including depression.
Highlights
Repressor element 1 silencing transcription factor (REST), known as neuron-restrictive silencing factor (NRSF), shows gene silencing transcription activities of target genes, which contain the repressor element-1 (RE-1) binding site (Calderone et al, 2003; Bruce et al, 2004; Schiffer et al, 2014)
Repressor element-1 silencing transcription factor (REST) gene expression was examined in seven brain regions of the Nile tilapia: telencephalon, pre-optic area, optic tectum, midbrain, hypothalamus, cerebellum, and hindbrain
All the brain regions showed over 20,000 copy numbers of REST mRNA
Summary
Repressor element 1 silencing transcription factor (REST), known as neuron-restrictive silencing factor (NRSF), shows gene silencing transcription activities of target genes, which contain the repressor element-1 (RE-1) binding site (Calderone et al, 2003; Bruce et al, 2004; Schiffer et al, 2014). REST Expression in 5-HT Neurons genes, in the specific brain regions and several brain diseases, including Alzheimer’s disease, Huntington disease, Parkinson’s disease, ischemia, epilepsy, and depression (Goswami et al, 2010; Baldelli and Meldolesi, 2015). Clinical study reports female depressed patients to show higher expression of REST gene in the dorsal raphe neurons (Goswami et al, 2010). In the serotonin (5-hydroxytryptamine, 5-HT) system, REST inhibitory effect regulates 5-HT1A receptor gene expression by binding to the RE-1 site in the 5-HT1A promoter region (Lemonde et al, 2004). Increased REST mRNA levels suppress 5-HT1A expression in the dorsal raphe of patients who suffer from depression (Goswami et al, 2010). The cellular localization of REST in neurons and astrocytes has been reported (Abrajano et al, 2009a,b; Prada et al, 2011; Pajarillo et al, 2020), the expression of REST in 5-HT neurons and their cellular function in 5-HT related mental disorders remain poorly understood
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