The effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate in different regions following hypoxic-ischemic brain injury in adult rats.

Abstract

Insulin-like growth factor-1 has pleiotropic effects in the central nervous system and can act both as a survival and a differentiation factor. Insulin-like growth factor-1 can be proteolytically cleaved into des-N-(1-3)-insulin-like growth factor-1 and a N-terminal tripeptide fragment, glycine-proline-glutamate. Both insulin-like growth factor-1 and des-N-(1-3)-insulin-like growth factor-1 can improve neuronal survival after hypoxic-ischemic brain injury in vivo. The present study investigates the effects of glycine-proline-glutamate on different brain regions and neuronal populations after hypoxic-ischemic injury. Unilateral hypoxic-ischemic injury was induced in adult rats. Glycine-proline-glutamate (3 microg) was administered centrally 2 h after the injury and the extent of brain damage determined five days later. In a separate trial immunohistochemical techniques were used to determine the effects of glycine-proline-glutamate on specific populations of neurons in the striatum after the injury. Compared to the vehicle treatment, glycine-proline-glutamate (n=19) treatment reduced the extent of cortical damage and neuronal loss in the CA1-2 subregions of the hippocampus (P<0.05). In the striatum, there was a trend towards a reduction in neuronal loss after glycine-proline-glutamate treatment (P=0.053) compared to the vehicle (n=21)-treated animals. In a separate study, glycine-proline-glutamate (n=8) treatment prevented the loss of choline acetyltransferase (P<0.05), glutamate acid decarboxylase (P<0.05) and somatostatin (P<0.05) containing neurons in the ipsilateral striatum following hypoxic-ischemic brain injury and also increased the numbers of neuronal nitric oxide synthase (P<0.05) containing neurons in the contralateral side. These studies suggest that in addition to neuroprotective effects, glycine-proline-glutamate can influence neuronal activity after hypoxic-ischemic injury.

• Authors: J Guan, H J Waldvogel, R L Faull, P D Gluckman, C E Williams
• Journal: Neuroscience (Neuroscience) Vol. 89 Issue 3 Pg. 649-59 (Mar 1999) ISSN: 0306-4522 [Print] United States
• PMID: 10199602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• Oligopeptides
• Somatostatin
• Insulin-Like Growth Factor I
• Choline O-Acetyltransferase
• Glutamate Decarboxylase
• glycyl-prolyl-glutamic acid

Topics

• Animals
• Brain Damage, Chronic (etiology, pathology)
• Brain Ischemia (complications, drug therapy)
• Choline O-Acetyltransferase (analysis)
• Corpus Striatum (pathology)
• Drug Evaluation, Preclinical
• Glutamate Decarboxylase (analysis)
• Hippocampus (pathology)
• Hypoxia, Brain (drug therapy)
• Insulin-Like Growth Factor I (pharmacology)
• Male
• Nerve Tissue Proteins (analysis)
• Neurons (chemistry)
• Oligopeptides (pharmacology)
• Rats
• Somatostatin (analysis)