Experimental Brain Research

, Volume 60, Issue 1, pp 27–37 | Cite as

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

  • B. A. Sabel
  • G. L. Dunbar
  • W. M. Butler
  • D. G. Stein
Article

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.

Key words

Gangliosides Brain lesions Behavioral recovery Neuronal reorganization 

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References

  1. Agnati LF, Fuxe K, Calza L, Benfenati F, Cavicchioli L, Toffano G, Goldstein M (1983) Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta Physiol Scand 119: 347–363Google Scholar
  2. Bernstein JJ, Gelderd JB, Bernstein ME (1974) Alteration of neuronal synaptic complement during regeneration and axonal sprouting of rat spinal cord. Exp Neurol 44: 470–482Google Scholar
  3. Björklund A, Stenevi U (1971) Growth of central catecholamine neurones into smooth mucle grafts in the rat mesencephalon. Brain Res 31: 1–20Google Scholar
  4. Buell SJ, Coleman PD (1979) Dendritic growth in the aged human brain and failure of growth in senile dementia. Science 206: 854–856Google Scholar
  5. Cotman CW, Nadler JV (1978) Reactive synaptogenesis in the hippocampus. In: Cotman CW (ed) Neuronal Plasticity. Raven Press, New York, pp 227–271Google Scholar
  6. Fass B, Ramirez JJ (1984) Effects of ganglioside treatments on lesion-induced behavioral impairments and sprouting in the CNS. J Neurosci Res 12: 445–458Google Scholar
  7. Firl A, Mufson EJ, Stein DG (1980) Silver impregnation of premounted neural tissue. Soc Neurosci Abstr, Cincinnatti, OhioGoogle Scholar
  8. Fishman PH, Brady RO (1976) Biosynthesis and function of gangliosides. Science 194: 906–915Google Scholar
  9. Glick SD, Jerussi TP, Fleisher LN (1976) Turning in circles: the neuropathology of rotation. Life Sci 18: 889–896Google Scholar
  10. Graybiel AM, Ragsdale CW (1979) Fiber connections of the basal ganglia. In: Cuenod M, Kreutzberg GW, Bloom FE (eds) Development and chemical specificity of neurons. Elsevier, Amsterdam, pp 239–283Google Scholar
  11. Karpiak SE (1983) Ganglioside treatment improves recovery of alternation behavior following unilateral entorhinal cortex lesions. Exp Neurol 81: 330–339Google Scholar
  12. Karpiak SE, Mahadik SP (1984) Reduction of cerebral edema with GM1 ganglioside. J Neurosci Res 12: 485–492Google Scholar
  13. Katzman R, Björklund A, Owman CH, Stenevi U, West KA (1971) Evidence for regenerative axon sprouting of central catecholamine neurons in the rat mesencephalon following electrolytic lesions. Brain Res 25: 579–596Google Scholar
  14. Land PW, Lund RD (1979) Development of the rat's uncrossed retinotectal pathway and its relationship to plasticity studies. Science 205: 698–700Google Scholar
  15. Marshall JF, Teitelbaum P (1974) Further analysis of sensory inattention following lateral hypothalamic damage in rats. J Comp Physiol Psychol 86: 375–395Google Scholar
  16. Mesulam MM (1978) Tetramethyl benzidine for horseradish-peroxidase neurohistochemistry: a non-carcinogenic blue reaction-product with superior sensitivity for visualizing neural afferents and efferents. J Histochem Cytochem 26: 106–117PubMedGoogle Scholar
  17. Oderfeld-Nowak B, Wöjcik M, Ulas J, Potempska A (1981) Effects of chronic ganglioside treatment on recovery processes in hippocampus after brain lesions in rats. In: Rapport MM, Gorio A (eds) Gangliosides in neurological and neuromuscular function, development, and repair. Raven Press, New York, pp 197–209Google Scholar
  18. Orlando P, Cocciante G, Ippolito G, Massari P, Roberti S, Tettamanti G (1979) The fate of tritium labelled GM1 ganglioside injected in mice. Pharmacol Res Commun 11: 759–773Google Scholar
  19. Pritzel M, Huston JP (1981) Neural and behavioral plasticity: crossed nigro-thalamic projections following unilateral substantia nigra lesions. Behav Brain Res 3: 393–399Google Scholar
  20. Pritzel M, Huston JP (1983a) Behavioral and neural plasticity following unilateral brain lesions. In: Myslobodsky MS (ed) Hemisyndromes: psychobiology, neurology, Academic Press, New York, pp 27–68Google Scholar
  21. Pritzel M, Huston JP, Sarter M (1983b) Behavioral and neuronal reorganization after unilateral substantia nigra lesions: evidence for increased interhemispheric nigrostriatal projections. Neuroscience 9: 879–888Google Scholar
  22. Sabel BA, Stein DG (1981) Extensive loss of subcortical neurons in the aging rat brain. Exp Neurol 73: 507–516Google Scholar
  23. Sabel BA, Slavin MD, Stein DG (1983) Enhancement of behavioral recovery from bilateral caudate lesions by gangliosides. Soc Neurosci Abstr: 243.9Google Scholar
  24. Sabel BA, Pritzel M, Morgan S, Huston JP (1984a) Interhemispheric nigro-thalamic projections and behavioral recovery following unilateral motor and sensory restriction. Exp Neurol 83: 49–61Google Scholar
  25. Sabel BA, Slavin MD, Stein DG (1984b) GM1-ganglioside treatment facilitates behavioral recovery from bilateral brain damage. Science 225: 340–342Google Scholar
  26. Sabel BA, Dunbar GL, Stein DG (1984c) Gangliosides minimize behavioral deficits and enhance structural repair after brain damage. J Neurosci Res 12: 429–443Google Scholar
  27. Sabel BA, Dunbar GL, Fass B, Stein DG (1985) Gangliosides, neuroplasticity, and behavioral recovery after brain damage. In: Will B, Schmitt P, Dalrymple-Alford JC (eds) Brain plasticity, learning and memory. New York, Plenum Press, pp 481–493Google Scholar
  28. Tettamanti G, Venerando B, Roberti S, Chigorno V, Sonnino S, Ghidoni R, Orlando P, Massari P (1981) The fate of exogenously administered brain gangliosides. In: Rapport MM, Gorio A (eds) Gangliosides in neurological and neuromuscular function, development, and repair. New York, Raven Press, pp 225–240Google Scholar
  29. Toffano G, Savoini GE, Moroni F, Lombardi MG, Calza L, Agnati LF (1983) GM1 ganglioside stimulates the regeneration of dopaminergic neurons in the central nervous system. Brain Res 261: 163–166Google Scholar
  30. Toffano G, Savoini GE, Moroni F, Lombardi G, Calza L, Agnati LF (1984a) Chronic GM1 ganglioside treatment reduces dopamine cell body degeneration in the substantia nigra after unilateral hemitransection in rat. Brain Res 296: 233–239Google Scholar
  31. Toffano G, Savoini G, Aporti F, Calzolari S, Consolazione A, Maura G, Marchi M, Raiteri M, Agnati LF (1984b) The functional recovery of damaged brain: the effects of GM1 monosialoganglioside. J Neurosci Res 12: 397–408Google Scholar
  32. Tupper DE, Wallace RB (1980) Utility of the neurological examination in rats. Acta Neurobiol Exp 40: 999–1003Google Scholar
  33. Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand Supp 367: 49–68PubMedGoogle Scholar
  34. Wójcik M, Ulas J, Oderfeld-Nowak B (1982) The stimulating effects of ganglioside injections on the recovery of choline acetyltransferase and acetylcholinesterase activities in the hippocampus of the rat after septal lesions. Neuroscience 7: 495–499Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • B. A. Sabel
    • 1
  • G. L. Dunbar
    • 1
  • W. M. Butler
    • 1
  • D. G. Stein
    • 1
    • 2
  1. 1.Department of PsychologyClark UniversityWorcesterUSA
  2. 2.Department of NeurologyUniversity of Massachusetts Medical CenterWorcesterUSA

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