Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat

Neurobiol Dis. 2011 Sep;43(3):588-97. doi: 10.1016/j.nbd.2011.05.007. Epub 2011 May 23.

Abstract

The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than in immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / physiology
  • Animals
  • Animals, Newborn
  • Antimanic Agents / toxicity
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / physiopathology
  • Female
  • Glucose Transporter Type 1 / genetics*
  • Glucose Transporter Type 3 / genetics*
  • Lithium Compounds / toxicity
  • Male
  • Monocarboxylic Acid Transporters / genetics*
  • Muscarinic Agonists / toxicity
  • Pilocarpine / toxicity
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus / genetics*
  • Status Epilepticus / metabolism*
  • Status Epilepticus / physiopathology
  • Symporters / genetics*

Substances

  • Antimanic Agents
  • Blood Glucose
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Lithium Compounds
  • Monocarboxylic Acid Transporters
  • Muscarinic Agonists
  • RNA, Messenger
  • Slc16a7 protein, rat
  • Slc2a1 protein, rat
  • Slc2a3 protein, rat
  • Symporters
  • monocarboxylate transport protein 1
  • Pilocarpine