Decreased plasma and cerebrospinal fluid content of neuroactive steroids in Parkinson's disease

The levels of the neuroactive steroids allopregnanolone (THP) and 5alpha-dihydroprogesterone (DHP) were quantified in the plasma of 11 (group 1) and in the liquor of 12 (group 2) Parkinson's disease (PD) patients using a gas-chromatographic/mass-spectrometric method. When compared with controls, both groups showed a significant decrease in DHP and THP concentrations. These decreases could be a useful marker of PD. Moreover, in view of the importance of GABA-ergic transmission to substantia nigra (SN) neurons and GABA-ergic modulation exerted by the two neuroactive steroids, our data indicate a global dysregulation of the SN GABA-ergic system in PD patients. Moreover, a lack of neuroprotective factors (i.e., GDNF, BDNF), promoted by DHP, may contribute to dopaminergic cell death.