Unique expression patterns of 5‐HT_2A and 5‐HT_2C receptors in the rat brain during postnatal development: Western blot and immunohistochemical analyses

Abstract

Serotonin (5-HT) is recognized as a potential regulatory factor in neuronal development. Two subtypes of receptors for it, 5-HT2A and 5-HT2C, are distributed broadly in the rat brain, suggesting their role in a variety of brain functions. Here, we investigated the expression patterns of these 5-HT2 receptors in the rat brain during postnatal development by using Western blot and immunohistochemical analyses. By Western blot analysis, the expression of the 5-HT2A receptor was at a low level at postnatal day 3 (P3) and increased greatly during the first 3 postnatal weeks; whereas the 5-HT2C receptor was already expressed at a high level at P3, and its expression increased only slightly during postnatal development. Immunohistochemical analysis showed the different expression patterns of 5-HT2A and 5-HT2C receptor subtypes during postnatal development: the transient expression of the 5-HT2C receptor was observed in layer IV of the somatosensory, visual, and auditory cortices from P10 to P28, and in the thalamus, mainly in the ventral posterolateral and ventral posteromedial nuclei, from P7 to P21; however, the immunoreactivity of the 5-HT2A receptor was detectable slightly at P3, but thereafter the intensity of immunolabeling increased with postnatal development and at P21 reached the adult level and pattern. These results suggest that 5-HT2 receptors have potential significance in brain development, with a functional difference between 5-HT2A and 5-HT2C receptor subtypes.

GPCR Modulation of Extrasynapitic GABAA Receptors

“…Among thalamic 5-HTRs (Mengod et al 2010), 5-HT 1A Rs and 5-HT 2A Rs, which are coupled to Gαq/G11-proteins and activate phospholipase C (PLC) β (Di Giovanni et al 2006), are relatively highly expressed in the GABAergic neurons of the NRT (Li et al 2004;Bonnin et al 2006;Rodriguez et al 2011). 5-HT 1A Rs are mainly present on the soma and proximal dendrites of these neurons, whereas 5-HT 2A R are less abundant and moderately expressed on cell bodies and more abundant on fine and medium-sized dendrite (Rodriguez et al 2011).…”

Central Serotonin2C Receptor: From Physiology to Pathology

“…In fact, 5-HT 2 receptors are major targets for a wide array of psychoactive drugs, ranging from non-classical antipsychotic drugs, anxiolytics and anti-depressants, which have a 5-HT 2 antagonistic action, to hallucinogens, which are agonists of the 5-HT 2 receptors [34][35][36][37]. Furthermore, recently it has been shown that 5-HT 2 receptors have a potential significance in brain development [38], and in experiencedependent plasticity in the visual cortex [39]. The 5-HT 2 receptor form a closely related subgroup of G-proteincoupled receptors and show the typical heptahelical structure of an integral membrane protein monomer.…”

“…This may relate to the inadequacy of techniques to determine the receptor in tissue samples. However, evidence from a variety of sources has involved this receptor in several important physiological and psychological processes including motor function, anxiety, ingestive behaviour and in brain development [33,38,[65][66][67]. 5-HT 2C receptor-deficient mice are overweight as a result of abnormal control of feeding behaviour [68,69], thus this receptor could play a role in the serotonergic control of appetite.…”

Developmental Changes in Serotonin 2C Receptor mRNA Editing in the Rat Cerebral Cortex and Primary Cultured Cortical Neurons

“…7) Moreover, it has been reported that the 5-HT2CR is not only involved in signal transduction, but also plays an important role in neuronal development. 2,12) We have demonstrated that blockade of 5-HT2CR by imipramine up-regulated 5-HT2C mRNA expression level and suppressed cell growth in a NG108-15 cell line. 13) Together, these findings allow us to infer that the 5-HT2CRs, probably some isomers, may be synthesized in the brain and contribute to neuronal growth and/or neuronal development.…”

“…[1][2][3] Messenger RNA of 5-HT2CR, as well as some other genes such as a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate receptor mRNA 4) and GABA A receptor a3 subunit mRNA, 5) undergoes adenosine-to-inosine (A-to-I) RNA editing 6) in their cording regions which are mediated by adenosine deaminases (ADARs). Burns et al 6) have identified five editing sites (named A, B, E (CЈ), C and D from the 5Ј-side) located in the 5-HT2C mRNA sequence encoding the second intracellular loop domain of 5-HT2CR (Fig.…”