Neurotrophin-4/5 selectively protects nigral calbindin-containing neurons in rats with medial forebrain bundle transections.

Abstract

Three neurotrophic factors associated with the nigrostriatal dopaminergic system were tested for their trophic potential to rescue degenerating substantia nigra dopaminergic neurons in adult rats with transections of the medial forebrain bundle. Axotomy of nigral dopaminergic neurons results in a retrograde degeneration of their cell bodies. Unilateral transections resulted in a partial reduction of the number of dopaminergic neurons as identified by immunocytochemistry for tyrosine hydroxylase to approximately half of the number of neurons present on the intact contralateral substantia nigra. A similar percentage loss was found for the subpopulation of nigral neurons which contain the calcium binding protein calretinin. In contrast, the small subpopulation of neurons which contain calbindin was less sensitive to the lesion and showed only mild loss in the number of cells, which was reduced to 87% of control. Neurotrophin-4/5, transforming growth factor alpha or basic fibroblast growth factor were infused supranigrally for two weeks after transection. None of the trophic factors tested reversed the loss of tyrosine hydroxylase-positive or calretinin-positive cells. In contrast, neurotrophin-4/5, but not transforming growth factor alpha or basic fibroblast growth factor, was found to reverse the axotomy-induced loss of calbindin-positive neurons and indeed increased the number of cells to 45% above control levels. In addition, neurotrophin-4/5 elevated the number of calbindin-containing neurons in intact unlesioned animals to 15% above control. These findings suggest that neurotrophin-4/5 selectively acts on nigral calbindin neurons following medial forebrain bundle transection and prevents these cells from degenerating.

• Authors: T Alexi, F Hefti
• Journal: Neuroscience (Neuroscience) Vol. 72 Issue 4 Pg. 911-21 (Jun 1996) ISSN: 0306-4522 [Print] United States
• PMID: 8735219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calb2 protein, rat
• Calbindin 2
• Calbindins
• Nerve Growth Factors
• Nerve Tissue Proteins
• Neuroprotective Agents
• S100 Calcium Binding Protein G
• Transforming Growth Factor alpha
• Fibroblast Growth Factor 2
• neurotrophin 5
• Tyrosine 3-Monooxygenase
• neurotrophin 4

Topics

• Animals
• Antibody Specificity
• Calbindin 2
• Calbindins
• Fibroblast Growth Factor 2 (pharmacology)
• Immunohistochemistry
• Injections, Intraventricular
• Male
• Nerve Growth Factors (pharmacology)
• Nerve Tissue Proteins (analysis, genetics)
• Neurons (chemistry, drug effects, enzymology)
• Neuroprotective Agents (pharmacology)
• Phenotype
• Prosencephalon (cytology, surgery)
• Rats
• Rats, Inbred F344
• S100 Calcium Binding Protein G (analysis, genetics, immunology)
• Substantia Nigra (cytology)
• Time Factors
• Transforming Growth Factor alpha (pharmacology)
• Tyrosine 3-Monooxygenase (analysis, genetics, immunology)