br Materials and Methods br Results br Discussion In the

Materials and Methods
Results
Discussion In the present study, we investigated the postnatal expression of the two GABA receptor subunits, GABAAα1 and GABAB1, in order to determine the differential expression and regional distribution pattern of them between right and left hippocampi in the rat during the first two weeks after birth. The techniques used were real-time PCR, western blot analysis, and immunohistochemistry. Taken together, the current results showed a relatively uniform left–right general expression of GABAAα1 and GABAB1, and there were only differences in hippocampal subregions. Finally, these GABA receptor subunits have already been expressed at birth, and then progressively increased at postnatal days 7 and 14. We focused on the first two postnatal weeks, a period of very active hippocampal-dentate neurogenesis (Humphrey, 1967). Furthermore, several studies demonstrated that hippocampal pyramidal neurons mainly formed before birth, and granule neurogenesis begins at embryonic days, and actively remains during the first postnatal weeks (Altman and Das, 1965; Hine and Das, 1974; Schlessinger et al., 1975; Thompson et al., 2008). Previous studies revealed the identifiable laterality differences in the volume of hippocampus and the morphology of hippocampal SB 258719 hydrochloride (Diamond et al., 1983; Förster et al., 2006; Toga and Thompson, 2003). In addition, it was reported several subtle but complex laterality differences in the developing hippocampus such as reports indicating fewer neurons in different right hippocampal subregions than the left one (Lister et al., 2006; Ragbetli et al., 2002). The present study was conducted to investigate the possible effects of GABA receptors, as an effective factor in the development of hippocampus, in the left-right asymmetry of hippocampus. For example, Hami et al. evaluated the expression of IGF-1 receptors as a trophic growth factor in the developing rat hippocampus to determine the differential expression of it between right and left hippocampi. They noted left-right asymmetry in IGF-1 with higher values at P7 in the right hippocampus, and at P14 in the left one (Hami et al., 2012). Similarly, Xiao et al. reported a laterality difference in androgen receptors in the rat hippocampus. They found higher number of androgen receptor positive cells on the left than the right, and suggested that may lead to literalities in hippocampal structure and function (Xiao and Jordan, 2002). In detailed studies have indicated that GABA receptors depolarize immature neurons, and play an excitatory effect (Ben-Ari, 2002; Cherubini et al., 1990; LoTurco et al., 1995; Meier et al., 2003; Schlesinger et al., 2004). Therefore, GABA is the major excitatory neurotransmitter before the maturation of glutamatergic synapses (Ben-Ari et al., 2007; Khazipov et al., 2001; Tyzio et al., 1999). This depolarization activates voltage-sensitive calcium channels that increase intracellular calcium. Thus, activates calcium-sensitive signaling processes (Ben-Ari, 2002; Owens et al., 1996; Reichling et al., 1994), which are essential for normal brain development through the control of DNA synthesis, proliferation, migration, and neuronal differentiation. In other words, the high levels of the GABA neurotransmitter during development may contributes to the proliferation of progenitor cells (Haydar et al., 2000), while the subsequent decrease interferes with proliferation (Antonopoulos et al., 1997; Haydar et al., 2000; LoTurco et al., 1995), raises the migration (Behar et al., 1996), and permits the neuronal differentiation. Precisely, in the hippocampus new neurons are generated from neural stem cells, and GABA receptors are expressed on these stem cells. Also, GABA can promote or suppress proliferation depending on the stage of development (Ben-Yaakov and Golan, 2003; Duveau et al., 2011; Giachino et al., 2014; Song et al., 2012). It has been noted that in the early developmental period, the maturation process of hippocampal neurons occurs up to GABAergic signaling switch to hyperpolarization mode, which is described in the immature pyramidal cells of rat hippocampus during the first postnatal weeks (Ben‐Ari et al., 1989). Accordingly, GABA receptors in the hippocampus may have an important role in neuronal plasticity underlying memory and learning (Benke, 2010).