Preventive effects of AdR-siPTEN through the regulation of NMDA receptor NR2B subunit in trigeminal ganglia of migraine rats

Neurol Res. 2012 Dec;34(10):998-1006. doi: 10.1179/1743132812Y.0000000113.

Abstract

Objective: Migraine is a refractory disease that is due to neuronal hyperexcitability, and has high incidence, mortality, and disability rates. The N-methyl-D-aspartate receptor 2B (NR2B) subunit has been found to play an important role in the pathogenesis of migraine. There is evidence suggesting that a tumor suppressor phosphatase and tensin homolog (PTEN) can confer a neuroprotective effect on cerebral ischemic injury by regulating NR2B levels. However, the role of PTEN in migraines is still unclear. This study aimed to define whether PTEN is involved in the pathogenesis of migraine through modulating NR2B, nitric oxide synthase (NOS), and nitric oxide (NO) in the trigeminal ganglia of rats with glyceryl trinitrate-induced migraine.

Methods: Adenovirus-expressing siPTEN or RFP was independently injected into the Sp5 (spinal trigeminal nucleus) of rats suffering from migraines. Seven days later, tactile sensory testing was performed to detect the tactile threshold. Immunofluorescence assay, western blot assay, RT-PCR, and biochemical examination were done to measure PTEN, NR2B, NOS, and NO levels in the trigeminal ganglia of migraine rats.

Results: NR2B, NOS, and NO levels significantly (P<0.05) decreased in the trigeminal ganglia of migraine-affected rats pretreated with adenovirus-expressing siPTEN.

Conclusion: These results suggest that PTEN in trigeminal ganglia is implicated in the pathogenesis of migraine, and PTEN may be a novel and promising candidate for future treatment and/or prevention of migraine via regulating NR2B and decreasing NO production in trigeminal ganglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Genetic Vectors / administration & dosage
  • Male
  • Migraine Disorders / genetics
  • Migraine Disorders / pathology
  • Migraine Disorders / prevention & control*
  • PTEN Phosphohydrolase / administration & dosage*
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Treatment Outcome
  • Trigeminal Ganglion / drug effects*
  • Trigeminal Ganglion / pathology

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • PTEN Phosphohydrolase
  • Pten protein, rat