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GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats.
J Neurol Sci 2002; 194(1):21-8JN

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<0.001), nerve conduction slowing (p<0.01) axonal and nodal structural changes (p<0.001), small myelinated fiber atrophy, and degenerative changes of C-fibers.

CONCLUSIONS

GCPII inhibition has beneficial effects on hyperalgesia, nerve function, and structural degenerative changes in DPN, which are likely mediated by inhibition of ischemia-induced glutamate release.

Authors+Show Affiliations

Department of Pathology, Wayne State University, 540 E. Canfield Ave, Detroit, MI 48201, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11809162

Citation

Zhang, W, et al. "GCPII (NAALADase) Inhibition Prevents Long-term Diabetic Neuropathy in Type 1 Diabetic BB/Wor Rats." Journal of the Neurological Sciences, vol. 194, no. 1, 2002, pp. 21-8.
Zhang W, Slusher B, Murakawa Y, et al. GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats. J Neurol Sci. 2002;194(1):21-8.
Zhang, W., Slusher, B., Murakawa, Y., Wozniak, K. M., Tsukamoto, T., Jackson, P. F., & Sima, A. A. (2002). GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats. Journal of the Neurological Sciences, 194(1), pp. 21-8.
Zhang W, et al. GCPII (NAALADase) Inhibition Prevents Long-term Diabetic Neuropathy in Type 1 Diabetic BB/Wor Rats. J Neurol Sci. 2002 Feb 15;194(1):21-8. PubMed PMID: 11809162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB/Wor rats. AU - Zhang,W, AU - Slusher,B, AU - Murakawa,Y, AU - Wozniak,K M, AU - Tsukamoto,T, AU - Jackson,P F, AU - Sima,A A F, PY - 2002/1/26/pubmed PY - 2002/3/30/medline PY - 2002/1/26/entrez SP - 21 EP - 8 JF - Journal of the neurological sciences JO - J. Neurol. Sci. VL - 194 IS - 1 N2 - 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<0.001), nerve conduction slowing (p<0.01) axonal and nodal structural changes (p<0.001), small myelinated fiber atrophy, and degenerative changes of C-fibers. CONCLUSIONS: GCPII inhibition has beneficial effects on hyperalgesia, nerve function, and structural degenerative changes in DPN, which are likely mediated by inhibition of ischemia-induced glutamate release. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/11809162/GCPII__NAALADase__inhibition_prevents_long_term_diabetic_neuropathy_in_type_1_diabetic_BB/Wor_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022510X01006700 DB - PRIME DP - Unbound Medicine ER -