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  • Developmental studies have reported that

    2022-05-21

    Developmental studies have reported that some subunits of GABAA receptors like α2 and α3 are predominantly expressed during in-utero development, and then substituted for α1 around birth in the rat hippocampus (Brooks-Kayal et al., 2001; Fritschy et al., 1994; Golshani et al., 1997; Kapur and Macdonald, 1999; Ramos et al., 2004; Temple and Wray, 2005). Lopez-Telleza et al. and Davis et al. stated that GABAAα1 receptor Cy5 NHS ester is low at birth and increases during the developmental period. They have reported P10 as the expression peak of GABAAα1 (Davis et al., 2000; Lopez-Tellez et al., 2004), and Laurie et al. determined P12 as such (Laurie et al., 1992). Our results were in line with them. Data obtained from real-time PCR and western blot revealed that expression of GABAAα1 at mRNA and protein levels have the same expressional pattern in the right and left hippocampi, and there were not significant laterality differences between them. Also, our results showed higher expression of GABAAα1 in the second week than the first week of the postnatal development. In this study, we found that the general expression of GABAAα1 subunit has the same expressional pattern in the right and left hippocampi, but there were several laterality differences in different subregions. The present immunohistochemical data showed that in the right hippocampus, OD of GABAAα1 progressively increase in all subregions from P0 until P14. At birth day, this OD was same across the hippocampus but at P7 and P14, the highest OD was observed in CA3. In contrast, in the left hippocampus, no marked changes in OD of GABAAα1 in CA2 area during the first two postnatal weeks were observed. In CA1 and CA3 subregions, there were not significant differences in OD from P0 until P7, but it showed a marked upregulation at P14. Also, in the left DG area, this increase was progressively during the two weeks. In addition, the highest OD in the left hippocampus during the first postnatal week was in CA2, although at P14 was in CA3. In the case of GABAB1 subunit, autoradiographic and immunohistochemical studies (Fritschy et al., 1999; Turgeon and Albin, 1994) demonstrated that GABAB receptors are expressed at high levels in the hippocampus during postnatal development. The present results have also shown that the expression of GABAB1 receptor subunit progressively increased during the first two postnatal weeks, and had the highest expression at P14. However, it was possible to increase if the assessment was longer, although López‐Bendito revealed that this high expression was followed by a considerable decrease at P15 (López‐Bendito et al., 2004). We found the same general expression of GABAB1 subunit between the right and left hippocampi, and there were only subtle differences in distributional pattern of it in different hippocampal subregions. So that, OD of GABAB1 subunit in the right hippocampus progressively increased during the first two postnatal weeks. But, in the left one, a significant increase was only observed in CA3 from P0 until P7, and then a marked upregulation at P14 in all hippocampal subregions. Moreover, the highest OD in the right hippocampus was observed in CA2, but in the left at P0 and P14 was in CA1. Unlike our findings, one study has generally shown enhanced GABA binding site in the left side (Guarneri et al., 1988).
    Declarations of interest
    Acknowledgement These data in this paper eventuated from results of Ph.D. thesis of Hoda Khoshdel Sarkarizi. Deputy Research of Mashhad University of medical science financially supported this research by the grant No. 94686.
    Introduction The ligand-gated ion channel family or more specifically cys-loop receptors are an important family of proteins which are targets for current insecticides and anthelmintics. Several of these receptors are targets for anthelmintics that are used to treat a variety of parasitic nematodes that infect animals including humans (Wolstenholme, 2011). The two most widely studied cys-loop receptors are the glutamate-gated chloride channels (GluCls) which are targets for macrocyclic lactone anthelmintics such as ivermectin and the nicotinic acetylcholine receptors which are targets for cholinergic anthelmintics such as levamisole (Holden-dye et al., 2014). However, the cys-loop receptor family of nematodes is quite large with several subtypes having no mammalian orthologues (Jones and Sattelle, 2008). This highlights their potential as targets for novel anthelmintics.