Parkinsonism-dementia complex (PDC) and amyotrophic lateral sclerosis (ALS) are fatal neurological diseases. The incidence on Guam was very high between 1950 and 1965 but decreased dramatically after 1965. It is thought that drinking water containing low levels of calcium (Ca) and magnesium (Mg), and high levels of aluminum and of a plant excitatory neurotoxin are involved in the pathogenesis of these diseases. The present experiment was performed in rats that were exposed to low Ca and/or Mg intake over two generations, thus simulating the conditions of human life on Guam, where several generations live continuously in the same environment. Significant loss of dopaminergic neurons was identified exclusively in the substantia nigra in 1-year-old rats that had been exposed continuously to low Mg intake (one-fifth of the normal level) over generations. The present study suggests that low Mg intake over generations may be involved in the pathogenesis of substantia nigra degeneration in humans.
Intraocular injections of ciliary neurotrophic factor (CNTF) or intraocular adenovirus-mediated CNTF gene transfer have been reported to inhibit retinal alterations in inherited retinal degeneration in mice strains. To investigate whether or not CNTF administered by eye drops prevents retinal degeneration in streptozotocin (STZ)-induced diabetic rats, recombinant CNTF was administered to eyes of diabetic rats (n=20) twice daily for 1 month after the onset of diabetes. The b-wave amplitude of electroretinogram in CNTF-administered diabetic rats was significantly larger than that of diabetic rats, and approached that of the controls. Atrophy of the inner plexiform layer, and cavity formation in the pigment epithelium, which were observed in diabetic rats, were prevented in CNTF-administered diabetic rats. These results indicate that CNTF administration by eye drops prevents retinal degeneration in STZ-induced diabetic rats.
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