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

Mech Ageing Dev. 1994 Aug;75(2):169-77. doi: 10.1016/0047-6374(94)90085-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Cerebellar Cortex / chemistry
  • Cerebellar Cortex / drug effects*
  • Immunohistochemistry
  • Male
  • Neurofilament Proteins / analysis
  • Neurofilament Proteins / drug effects*
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Calcium Channel Blockers
  • Neurofilament Proteins
  • Nifedipine
  • darodipine