GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats

W. Zhang, Barbara Slusher, Y. Murakawa, K. M. Wozniak, Takashi Tsukamoto, P. F. Jackson, A. A F Sima

Research output: Contribution to journalArticle

Abstract

Aims/Hypothesis: Hyperglutamatergic activity induced by ischemia is believed to underlie neuronal damage in a variety of neurological disorders, including neuropathic pain. Since ischemia is believed to be a prominent mechanism involved in diabetic polyneuropathy (DPN), we investigated the effect of the glutamate carboxypeptidase II (GCPII, EC #3.4-17.21; previously termed NAALADase), an enzyme responsible for the hydrolysis of the neuropeptide NAAG to NAA and glutamate, on the development of DPN in type 1 diabetic BB/Wor rats. Methods: Diabetic animals were treated with 10 mg/kg/day i.p. of the selective GCPII inhibitor GPI-5232 from onset of diabetes for 6 months. Hyperalgesia to thermal stimulation and nerve conduction velocity (NCV) were measured monthly. The effect on structural DPN was assessed by scoring of single, teased myelinated fibers, myelinated fiber morphometry and ultrastructural examination of C-fibers at 6 months. Results: GCPII inhibition showed significant but partial effects on hyperalgesia (p

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalJournal of the Neurological Sciences
Volume194
Issue number1
DOIs
StatePublished - Feb 15 2002
Externally publishedYes

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Glutamate Carboxypeptidase II
Inbred BB Rats
Diabetic Neuropathies
Hyperalgesia
Ischemia
Unmyelinated Nerve Fibers
Neural Conduction
Neuralgia
Nervous System Diseases
Neuropeptides
Glutamic Acid
Hydrolysis
Enzymes

Keywords

  • GCPII inhibition
  • Glutamate
  • Hyperalgesia
  • NAAG
  • Nerve conduction
  • Neuropathy
  • Pathology

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats. / Zhang, W.; Slusher, Barbara; Murakawa, Y.; Wozniak, K. M.; Tsukamoto, Takashi; Jackson, P. F.; Sima, A. A F.

In: Journal of the Neurological Sciences, Vol. 194, No. 1, 15.02.2002, p. 21-28.

Research output: Contribution to journalArticle

Zhang, W. ; Slusher, Barbara ; Murakawa, Y. ; Wozniak, K. M. ; Tsukamoto, Takashi ; Jackson, P. F. ; Sima, A. A F. / GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats. In: Journal of the Neurological Sciences. 2002 ; Vol. 194, No. 1. pp. 21-28.
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