Metabolic environment in substantia nigra reticulata is critical for the expression and control of hypoglycemia-induced seizures

Libor Velíšek, Jana Velíšková, Ondřej Chudomel, Ka Lai Poon, Kimberly Robeson, Barbara Marshall, Archana Sharma, Solomon L. Moshé

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Seizures represent a common and serious complication of hypoglycemia. Here we studied mechanisms of control of hypoglycemic seizures induced by insulin injection in fasted and nonfasted rats. We demonstrate that fasting predisposes rats to more rapid and consistent development of hypoglycemic seizures. However, the fasting-induced decrease in baseline blood glucose concentration cannot account for the earlier onset of seizures in fasted versus nonfasted rats. Data obtained with c-Fos immunohistochemistry and [14C]2-deoxyglucose uptake implicate a prominent involvement of the substantia nigra reticulata (SNR) among other structures in the hypoglycemic seizure control. This is supported by data showing that fasting decreases the SNR expression of K ATP channels, which link metabolism with activity, and is further confirmed with microinfusions of KATP channel agonist and antagonist. Data obtained with whole-cell and perforated patch recordings from SNR neurons in slices in vitro demonstrate that both presynaptic and postsynaptic K ATP channels participate in the failure of the SNR to control hypoglycemic seizures. The results suggest that fasting and insulin-induced hypoglycemia can lead to impairment in the function of the SNR, leading thus to hypoglycemic seizures.

Original languageEnglish (US)
Pages (from-to)9349-9362
Number of pages14
JournalJournal of Neuroscience
Volume28
Issue number38
DOIs
StatePublished - Sep 17 2008

Keywords

  • 2-deoxyglucose
  • Fasting
  • Hypoglycemia
  • Intracellular recordings
  • Kir6.2
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

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