Functional Activity of Substantia Nigra Grafts Reinnervating the Striatum: Neurotransmitter Metabolism and ( 14 C)2‐Deoxy‐ d ‐glucose Autoradiography

Functional Activity of Substantia Nigra Grafts Reinnervating the Striatum: Neurotransmitter... 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 caudateputamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudateputamen 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 transplantreinnervated 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. 6‐Hydroxydopamine denervation of the caudate‐putamen had no significant effect on neuronal metabolism in that region, nor did subsequent reinnervation from a graft. Grafts, however, were associated with a 16% reduction of glucose uptake in the ipsilateral globus pallidus, indicating a significant transsynaptic influence of the nigral transplants on neuronal metabolism in the host brain. 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 trans‐plants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6‐hydroxydopamine lesion. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Functional Activity of Substantia Nigra Grafts Reinnervating the Striatum: Neurotransmitter Metabolism and ( 14 C)2‐Deoxy‐ d ‐glucose Autoradiography

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Publisher
Wiley
Copyright
Copyright © 1982 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1982.tb08693.x
Publisher site
See Article on Publisher Site

Abstract

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 caudateputamen and were screened for rotational behavior following 5 mg/kg methamphetamine. The grafts restored dopamine concentrations in the caudateputamen 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 transplantreinnervated 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. 6‐Hydroxydopamine denervation of the caudate‐putamen had no significant effect on neuronal metabolism in that region, nor did subsequent reinnervation from a graft. Grafts, however, were associated with a 16% reduction of glucose uptake in the ipsilateral globus pallidus, indicating a significant transsynaptic influence of the nigral transplants on neuronal metabolism in the host brain. 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 trans‐plants can reinstate dopaminergic neurotransmission in regions of the host brain initially denervated by the 6‐hydroxydopamine lesion.

Journal

Journal of NeurochemistryWiley

Published: Mar 1, 1982

References

  • A simple radioenzymatic method for determination of picogram amounts of 3,4‐dihydroxyphenylacetic acid (DOPAC) in the rat brain
    Argiolas, Argiolas; Fadda, Fadda; Stefanini, Stefanini; Gessa, Gessa
  • Reformation of the severed septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons
    Bjorklund, Bjorklund; Stenevi, Stenevi
  • Functional reinnervation of the neostriatum in the adult rat by use of intraparenchymal grafting of dissociated cell suspensions from the substantia nigra
    Bjöklund, Bjöklund; Schmidt, Schmidt; Stenevi, Stenevi
  • Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: Long‐term behavioral, biochemical and histochemical studies
    Freed, Freed; Perlow, Perlow; Karoum, Karoum; Seiger, Seiger; Olson, Olson; Hoffer, Hoffer; Wyatt, Wyatt
  • Differentiation of embryonic hypothalamic transplants cultured on the choroidal pia in brains of adult rats
    Stenevi, Stenevi; Björklund, Björklund; Kromer, Kromer; Paden, Paden; Gerlach, Gerlach; McEwen, McEwen; Silverman, Silverman
  • Radioenzymatic assay of femtomole concentrations of dopa in tissues and body fluids
    Zurcher, Zurcher; Prada, Prada

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