Temporal and topographic alterations in expression of the alpha3 isoform of Na+, K(+)-ATPase in the rat freeze lesion model of microgyria and epileptogenesis

Neuroscience. 2009 Aug 18;162(2):339-48. doi: 10.1016/j.neuroscience.2009.04.003. Epub 2009 Apr 9.

Abstract

Na(+),K(+)-ATPase contributes to the asymmetrical distribution of sodium and potassium ions across the plasma membrane and to maintenance of the membrane potential in many types of cells. Alterations in this protein may play a significant role in many human neurological disorders, including epilepsy. We studied expression of the alpha3 isoform of Na(+),K(+)-ATPase in the freeze lesion (FL) microgyrus model of developmental epileptogenesis to test the hypothesis that it is downregulated following neonatal cortical injury. FL and sham-operated rat brains were examined at postnatal day (P)7, P10, P14, P21-28 and P50-60 after placement of a transcranial freeze lesion at P0 or P1. Immunohistochemistry and in situ hybridization were used to assess the expression of the alpha3 isoform of Na(+),K(+)-ATPase (termed alpha3, or alpha3 subunit below) in neuropil and the perisomatic areas of pyramidal cells and parvalbumin-containing interneurons. There was a significant decrease (P<0.05) in alpha3 subunit immunoreactivity (IR) in the neuropil of FL cortical layer V of the P14 and P21-28 groups that extended up to 360 mum from the border of the microgyrus, an area that typically exhibits evoked epileptiform activity. Alpha-3 was decreased in the perisomatic area of pyramidal but not parvalbumin-containing cells in P21-28 FL animals. A reduction in alpha3 mRNA was observed in the neuropil of FL cortical layer V up to 1610 mum from the microgyral edge. The developmental time course for expression of the alpha3 subunit between P7 and P60 was examined in naive rat cortices and results showed that there was a significant increase in alpha3 IR between P7 and P10. The significant decreases in Na(+),K(+)-ATPase in the paramicrogyral cortex may contribute to epileptogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology*
  • Brain / growth & development
  • Brain / pathology
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Epilepsy / enzymology*
  • Epilepsy / pathology
  • Freezing
  • Interneurons / enzymology
  • Isoenzymes / biosynthesis
  • Malformations of Cortical Development / enzymology*
  • Malformations of Cortical Development / pathology
  • Pyramidal Cells / enzymology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / biosynthesis*

Substances

  • Isoenzymes
  • RNA, Messenger
  • Atp1a3 protein, rat
  • Sodium-Potassium-Exchanging ATPase