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Brain Res. 2011 May 10;1389:61-70. doi: 10.1016/j.brainres.2011.02.083. Epub 2011 Mar 4.

The developmental changes of Na(v)1.1 and Na(v)1.2 expression in the human hippocampus and temporal lobe.

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Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.


Alterations of the genes encoding α1 and α2 subunits of voltage-gated sodium channels (SCN1A, SCN2A) have been reported as causes of various types of epilepsy, most of which occur during the first year of life; as yet, however, the detailed mechanisms are unclear. We suppose that developmental changes of SCN1A and SCN2A in the human brain, which are unknown yet, may play an important role. So here, we studied the developmental changes of their corresponding proteins (Na(v)1.1 and Na(v)1.2) in the human hippocampus and temporal lobe in 28 autopsy cases, which age from 13weeks of gestation (GW) to 63years of age (Y). Using comparative microscopic immunohistochemical (IHC) analysis, we found that Na(v)1.1 and Na(v)1.2 immunoreactivity first appeared at 19GW, simultaneously in the hippocampus and the white matter of temporal lobe. In nearly all age groups, Na(v)1.1 immunoreactivity was weak and relatively homogeneous. In general, Na(v)1.1 immunoreactive (IR) neurons and neurites increased during the late fetal and postnatal periods, reached their peaks 7-9months after birth (M), then decreased and remained stable at a relatively low level during childhood and adulthood. On the other hand, Na(v)1.2 immunoreactivity was strong and heterogeneous. In the hippocampus, Na(v)1.2 IR neurons increased gradually during the late fetal period, reached their peaks at 7-9M, sustained this high level during childhood, and then decreased slightly at adulthood. In the temporal lobe, Na(v)1.2 IR neurons reached a high level during the late fetal period, and maintained that level during subsequent developmental stages; Na(v)1.2 IR neurites also increased to a relatively high level during the late fetal period and continued to increase up to and during adulthood. Using double-staining IHC, we found that Na(v)1.1 and Na(v)1.2 had a relatively high colocalization rate with parvalbumin and showed distinct developmental changes. These findings extend our previous understanding of sodium channels and may help us discover the pathomechanisms of sodium channel-related age-dependent epilepsy.

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