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Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats]

Journal Article:

Abstract

Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by (14C)deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. Overall the  More>>
Publication Date:
Mar 01, 1982
Product Type:
Journal Article
Reference Number:
EDB-82-098142
Resource Relation:
Journal Name: J. Neurochem.; (United Kingdom); Journal Volume: 38:3
Subject:
59 BASIC BIOLOGICAL SCIENCES; BRAIN; PHYSIOLOGY; DOPA; METABOLISM; DOPAMINE; GRAFTS; BIOLOGICAL FUNCTIONS; AUTORADIOGRAPHY; BEHAVIOR; CARBON 14 COMPOUNDS; GLUCOSE; RATS; ALDEHYDES; AMINES; AMINO ACIDS; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARBOHYDRATES; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; CENTRAL NERVOUS SYSTEM; DRUGS; FUNCTIONS; HEXOSES; HYDROXY ACIDS; HYDROXY COMPOUNDS; LABELLED COMPOUNDS; MAMMALS; MONOSACCHARIDES; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PHENOLS; POLYPHENOLS; RODENTS; SACCHARIDES; SYMPATHOMIMETICS; TRANSPLANTS; VERTEBRATES; 551001* - Physiological Systems- Tracer Techniques
OSTI ID:
5390130
Research Organizations:
Department of Histology, University of Lund, Sweden
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: CODEN: JONRA
Submitting Site:
HEDB
Size:
Pages: 737-748
Announcement Date:

Journal Article:

Citation Formats

Schmidt, R H, Ingvar, M, Lindvall, O, Stenevi, U, and Bjoerklund, A. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats]. United Kingdom: N. p., 1982. Web.
Schmidt, R H, Ingvar, M, Lindvall, O, Stenevi, U, & Bjoerklund, A. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats]. United Kingdom.
Schmidt, R H, Ingvar, M, Lindvall, O, Stenevi, U, and Bjoerklund, A. 1982. "Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats]." United Kingdom.
@misc{etde_5390130,
title = {Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and (14C)2-deoxy-D-glucose autoradiography. [Rats]}
author = {Schmidt, R H, Ingvar, M, Lindvall, O, Stenevi, U, and Bjoerklund, A}
abstractNote = {Dopaminergic innervation of the caudate nucleus in adult rats can be partially restored by the grafting of embryonic substantia nigra into the overlying parietal cortex with concomitant compensation of certain behavioral abnormalities. In this study the function of such grafts was investigated neurochemically by quantification of transmitter metabolism and glucose utilization in the reinnervated target. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle received a single graft to the dorsal caudate-putamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudate-putamen from initially less than 0.5% to an average of 13.6% of normal in rats with behavioral compensation. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine, which is a measure of the rate of transmitter turnover, were equivalent in transplanted and normal control rats. Moreover, measurements of DOPA accumulation for a 30-min period after DOPA decarboxylase inhibition indicated similar fractional dopamine turnover rates in normal and transplant-reinnervated tissues. Correlations between rotational behavior and dopamine concentrations showed that reinnervation to only 3% of normal was sufficient to counterbalance the motor asymmetry. Measurements of glucose utilization by (14C)deoxyglucose autoradiography indicated equivalent metabolic rates for the grafted tissue and the intact substantia nigra. Overall the results indicate that behaviorally functional neuronal grafts spontaneously metabolize dopamine and utilize glucose at rates characteristic of the intact nigrostriatal system. This provides further evidence that ectopic intracortical nigral transplants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6-hydroxydopamine lesion.}
journal = {J. Neurochem.; (United Kingdom)}
volume = {38:3}
journal type = {AC}
place = {United Kingdom}
year = {1982}
month = {Mar}
}