Insulin-like growth factor-I improves cerebellar dysfunction but does not prevent cerebellar neurodegeneration in the calcium channel mutant mouse, leaner.
The effects of insulin-like growth factor-I (IGF-I) on cerebellar dysfunction and neurodegeneration were investigated in leaner mice, which exhibit cerebellar ataxia and neurodegeneration related to P/Q-type calcium channel mutations. Leaner mice showed significantly reduced serum and cerebellar IGF-I concentrations compared to wild-type mice at postnatal day 30. Behavioral assessment of leaner mice injected with IGF-I subcutaneously for 4 weeks showed partially improved cerebellar function. Histological analysis of IGF-I treated leaner cerebella showed no difference in the number of dying Purkinje cells compared to control leaner cerebella. These results further support potential use of IGF-I as a therapeutic aid for cerebellar ataxia related to calcium channel mutations. Nonetheless, IGF-I administration does not rescue dying cerebellar neurons, which suggests that the beneficial effects of IGF-I may have been achieved through surviving cerebellar neurons.
Nahm
Sang-Soep
SS
Department of Veterinary Anatomy & Public Health, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4458, USA.
Frank
Tamy C
TC
Browning
Michelle D
MD
Sepulvado
Jarita M
JM
Hiney
Jill K
JK
Abbott
Louise C
LC
D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000172:deficiency* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D013132:Spinocerebellar Degenerations / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D015220:Calcium Channels; D007334:Insulin-Like Growth Factor I