Effects of Selegiline in a retroviral rat model for neurodegenerative disease

Upon inoculation into neonatal rats, murine leukemia virus (MuLV) NT40 caus es a non-inflammatory degeneration of the central nervous system, While mic roglia cells appear to be the major target cells within the brain parenchym a for neurovirulent MuLV, degenerating neurons do not express retroviral ge ne products. In order to protect rats fi om neuronal damage we treated retr ovirally infected rats once with monoamine oxidase (MAO) B inhibitor Selegi line which - under different conditions - exerts neuroprotective effects. U nexpectedly, when administered at 17 days post-infection (d.p.i.) a single intraperitoneal dose of Selegilin (1 mg/kg body-eight) significantly shorte ned the incubation period for neurological disease. In contrast, Selegiline given in a lower dosage (0.05 mg/kg bodyweight) and/or at a different time point (13 d.p.i.) at the low (0.05 mg/kg bodyweight) and the high dose (1. 0 mg/kg bodyweight) had no effect on the outcome of neurological disease. A nimals treated with Selegiline (1.0 mg/kg bodyweight at 17 d.p.i.) containe d higher amounts of viral loads in the CNS. higher numbers of brain cells e xpressing major histocompatibility complex class II molecules, and exhibite d inhibition of MAO-B in comparison to untreated yet infected (control) ani mals. Supposedly, Selegiline activated the major target cell population of the CNS for MuLV-NT40, microglia, with the consequence of enhanced suscepti bility for retroviral infection and triggered endogenous mechanism(s) invol ved in the pathogenesis of retroviral neurodegeneration.