Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of neurofilament protein immunoreactivity in the cerebellar cortex of aged rats.

The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist darodipine (PY 108-068) on the expression of neurofilament (NF) protein (200 kDa-NF subunit) immunoreactivity in the cerebellar cortex of aged male Wistar rats was assessed using immunohistochemical techniques associated with image analysis. In 12-month-old rats (adult) used as reference animals, 200 kDa-NF subunit immunoreactivity was observed primarily in axons of basket neurons localized in the molecular layer and surrounding the cell body of Purkinje neurons. A specific immunoreactivity was also found in the initial segment of Purkinje neuron axons, and in axons of the white matter of the cerebellar cortex. In 24-month-old rats (aged) a significant decrease in the area occupied by immunoreactive structures was noticeable in comparison with adult animals. A 6-month treatment (from the 18th to the 24th month of life) with an oral daily dose of 10 mg/kg of darodipine restored in part the expression of 200 kDa-NF subunit immunoreactivity in the cerebellar cortex. These data indicate that treatment with the dihydropyridine-type Ca2+ channel blocker darodipine is able to counter in part the age-related loss in the expression of NF protein in the rat cerebellar cortex. This suggests that darodipine may reduce neuronal cytoskeletal changes occurring in aging and in neurodegenerative disorders.