GM1 gangliosides stimulate neuronal reorganization and reduce rotational asymmetry after hemitransections of the nigro-striatal pathway

GM1 gangliosides stimulate neuronal reorganization and reduce rotational asymmetry after... 221 60 60 1 1 B. A. Sabel G. L. Dunbar W. M. Butler D. G. Stein Department of Psychology Clark University 01610 Worcester MA USA Department of Neurology University of Massachusetts Medical Center 01605 Worcester MA USA Department of Psychology and Brain Science E25-634 Massachusetts Institute of Technology 02139 Cambridge MA USA Summary The effects of monosialoganglioside (GM1) injections on neuronal reorganization and behavioral recovery were studied in rats with unilateral transections of the nigro-striatal pathway. In Experiment 1, animals were treated daily with injections of saline or GM1 for not more than 14 days. At 2 days after surgery, GM1-treated animals exhibited less amphetamine-induced rotational asymmetry than did saline treated counterparts. This difference was still apparent at day 12, but vanished at post-operative day 39. Apomorphine-induced rotational asymmetry was equal in both groups at day 15, but by day 42, asymmetries increased in saline controls while remaining unchanged in GM1-treated animals. Rats were killed at either post-operative days 3, 15, or 45 after having received injections of horseradish peroxidase (HRP) into the denervated caudate nucleus. The number of neurons labelled by retrograde HRP-transport were counted in the ipsilateral substantia nigra pars compacta (iSNc), ipsilateral ventral tegmental area (iVTA), frontal cortex, and in the contralateral substantia nigra pars compacta (cSNc). Anterograde transport was also examined in the ipsilateral substantia nigra pars reticulata (iSNr). A significant loss of retrograde labelling in iSNc and iVTA was observed for both groups at post-operative day 3. At day 15, however, GM1-treated animals showed more labelling in these structures as well as in the cSNc. At 45 days after surgery comparable labelling was seen in both lesion groups. The total area of anterograde HRP-labelling in the iSNr significantly increased over time, with no differences between treatment groups. In Experiment 2, rats given the same hemitransections as in Experiment 1, were treated with daily injections of saline or GM1 for 14 days, and then received unilateral injections of 6-hydroxydopamine into the iSNc and iVTA. Nine days later, brain tissue was stained for examination of anterograde degeneration. Significantly more degenerating axons and terminals were found in the caudate nucleus of GM1-treated rats than in salinetreated controls. We propose that the early reduction of behavioral deficits may be related to a ganglioside-induced reduction of secondary degeneration or edema. The effect of gangliosides on later behavioral recovery is to accelerate neuronal reorganization. This reorganization probably involves terminal proliferation of ascending, intact striatal afferents spared by the hemitransection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Brain Research Springer Journals

GM1 gangliosides stimulate neuronal reorganization and reduce rotational asymmetry after hemitransections of the nigro-striatal pathway

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Publisher
Springer Journals
Copyright
Copyright © 1985 by Springer-Verlag
Subject
Biomedicine; Neurosciences; Neurology
ISSN
0014-4819
eISSN
1432-1106
D.O.I.
10.1007/BF00237015
Publisher site
See Article on Publisher Site

Abstract

221 60 60 1 1 B. A. Sabel G. L. Dunbar W. M. Butler D. G. Stein Department of Psychology Clark University 01610 Worcester MA USA Department of Neurology University of Massachusetts Medical Center 01605 Worcester MA USA Department of Psychology and Brain Science E25-634 Massachusetts Institute of Technology 02139 Cambridge MA USA Summary The effects of monosialoganglioside (GM1) injections on neuronal reorganization and behavioral recovery were studied in rats with unilateral transections of the nigro-striatal pathway. In Experiment 1, animals were treated daily with injections of saline or GM1 for not more than 14 days. At 2 days after surgery, GM1-treated animals exhibited less amphetamine-induced rotational asymmetry than did saline treated counterparts. This difference was still apparent at day 12, but vanished at post-operative day 39. Apomorphine-induced rotational asymmetry was equal in both groups at day 15, but by day 42, asymmetries increased in saline controls while remaining unchanged in GM1-treated animals. Rats were killed at either post-operative days 3, 15, or 45 after having received injections of horseradish peroxidase (HRP) into the denervated caudate nucleus. The number of neurons labelled by retrograde HRP-transport were counted in the ipsilateral substantia nigra pars compacta (iSNc), ipsilateral ventral tegmental area (iVTA), frontal cortex, and in the contralateral substantia nigra pars compacta (cSNc). Anterograde transport was also examined in the ipsilateral substantia nigra pars reticulata (iSNr). A significant loss of retrograde labelling in iSNc and iVTA was observed for both groups at post-operative day 3. At day 15, however, GM1-treated animals showed more labelling in these structures as well as in the cSNc. At 45 days after surgery comparable labelling was seen in both lesion groups. The total area of anterograde HRP-labelling in the iSNr significantly increased over time, with no differences between treatment groups. In Experiment 2, rats given the same hemitransections as in Experiment 1, were treated with daily injections of saline or GM1 for 14 days, and then received unilateral injections of 6-hydroxydopamine into the iSNc and iVTA. Nine days later, brain tissue was stained for examination of anterograde degeneration. Significantly more degenerating axons and terminals were found in the caudate nucleus of GM1-treated rats than in salinetreated controls. We propose that the early reduction of behavioral deficits may be related to a ganglioside-induced reduction of secondary degeneration or edema. The effect of gangliosides on later behavioral recovery is to accelerate neuronal reorganization. This reorganization probably involves terminal proliferation of ascending, intact striatal afferents spared by the hemitransection.

Journal

Experimental Brain ResearchSpringer Journals

Published: Sep 1, 1985

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