Abstract

The present study was carried out to investigate neuroprotective effects of the autophagy inducer rapamycin against low and high concentrations of rotenone in primary dopaminergic cell culture.
Cultures prepared from embryonic mouse mesencephala were treated on the 10th DIV with different concentrations of rotenone (10, 20 nM) and rapamycin (1, 10, 100, 1000 nM) for 48 h. On the 12th DIV, cultures were stained immunocytochemically using tyrosine hydroxylase antibody. Rotenone significantly reduced the number of dopamine neurons/their neurites by 22/33% and 40/60% at the concentrations of 10 and 20 nM, respectively. On the other hand, rapamycin was seen to completely reverse rotenone’s effect on the number of dopamine neurons at the 10 nM rotenone while it rescued only 17% in cultures treated with 20 nM of rotenone. Moreover, rapamycin caused much more attenuation in the loss of cell neurites in cultures treated with 10 nM rotenone (57%) than those treated with 20 nM rotenone (48%). In conclusion, rapamycin produces much protection against low rotenone concentration on dopamine neurons. This effect might be attributed to the efficacy of the autophagy process induced by rapamycin in repairing slightly damaged dopamine neurons by low rotenone concentration.

Key words: dopamine neurons, neurodegeneration, Parkinson’s disease, pesticides, rapamycin, rotenone