Effects of Selegiline in a retroviral rat model for neurodegenerative disease.
Upon inoculation into neonatal rats, murine leukemia virus (MuLV) NT40 causes a non-inflammatory degeneration of the central nervous system. While microglia cells appear to be the major target cells within the brain parenchyma for neurovirulent MuLV, degenerating neurons do not express retroviral gene products. In order to protect rats from neuronal damage we treated retrovirally infected rats once with monoamine oxidase (MAO) B inhibitor Selegiline which--under different conditions--exerts neuroprotective effects. Unexpectedly, when administered at 17 days post-infection (d.p.i.) a single intraperitoneal dose of Selegilin (1 mg/kg bodyweight) significantly shortened 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. Animals treated with Selegiline (1.0 mg/kg bodyweight at 17 d.p.i.) contained higher amounts of viral loads in the CNS, higher numbers of brain cells expressing major histocompatibility complex class II molecules, and exhibited inhibition of MAO-B in comparison to untreated yet infected (control) animals. Supposedly, Selegiline activated the major target cell population of the CNS for MuLV-NT40, microglia, with the consequence of enhanced susceptibility for retroviral infection and triggered endogenous mechanism(s) involved in the pathogenesis of retroviral neurodegeneration.
Czub
M
M
Institut für Virologie, Universität Wurzburg, Germany.
Czub
S
S
Gosztonyi
G
G
Koutsilieri
E
E
Sopper
S
S
Müller
J G
JG
Gerlach
M
M
Riederer
P
P
ter Meulen
V
V
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000821:virology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000517:prevention & control / Q000821:virology*; D012367:RNA, Viral / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012192:Retroviridae Infections / Q000378:metabolism / Q000517:prevention & control / Q000821:virology*; D012642:Selegiline / Q000633:toxicity*; D014412:Tumor Virus Infections / Q000378:metabolism / Q000517:prevention & control / Q000821:virology*
D000949:Histocompatibility Antigens Class II; D008996:Monoamine Oxidase Inhibitors; D012367:RNA, Viral; D012642:Selegiline