The seizure-related gene 6 (Sez-6) encodes a transmembrane protein that is expressed in neuronal cells. A Sez-6-deficient mouse exhibits impaired spatial memory, motor deficits, and decreased anxiety levels. To understand the function of Sez-6 during the postnatal development of the forebrain, the spatiotemporal pattern of distribution of the Sez-6 protein was immunohistochemically analyzed using a new anti-Sez-6 antibody. Western blot analysis confirmed the specificity of this new antibody, and showed that the content of the Sez-6 protein in the cerebral cortex was highest during the neonatal period and decreased gradually thereafter. Immunohistochemical analysis revealed that Sez-6 immunoreactivity (IR) was detected in various brain regions, such as the hippocampus, cerebral cortex, piriform cortex, striatum, lateral amygdala, and olfactory tubercle. The expression patterns of Sez-6 in these brain regions was divided into three groups: i) in the cerebral cortex, hippocampus, and lateral amygdala, moderate-to-strong Sez-6 IR was detected in the first postnatal week and decreased gradually thereafter; ii) Sez-6 IR was not observed during the neonatal period in the striatum and the intensity of the signal increased gradually toward adulthood; and iii) strong Sez-6 IR was observed in the olfactory tubercle, regardless of the developmental stage. Furthermore, Sez-6 IR was detected in dendrites of hippocampal and cortical pyramidal neurons neonatally, whereas it localized around the soma after postnatal day 10. These spatiotemporal alterations of the regional and intracellular distribution of the Sez-6 protein suggest multiple functions for this protein during the postnatal development of the forebrain.
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