Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson's disease.
The pathological process of neurodegeneration, which is observed in Alzheimer's (AD) and Parkinson's (PD) diseases and that follows any insult to the central nervous system, is accompanied by an inflammatory reaction, which is believed to contribute to the pathogenesis of the diseases. In accordance to this, the anti-inflammatory agents are suggested to be effective in slowing or inhibiting the degenerative process. In this study, we investigated the influence of dexamethasone (DXM) on the nigrostriatal dopaminergic neurons damage following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP). Mice C57BL received pre-treatment of the various doses of dexamethasone followed by MPTP administration (40 mg/kg). We found that dexamethasone 1 mg/kg diminished a dopamine content depletion in striatum by about 20%, when the doses of 0.1 mg/kg was ineffective and 10 mg/kg even aggravate the dopamine content decrease. In the second step of the experiment, we chose the effective doses, 1 mg/kg, and started the treatment before and 24 h after MPTP administration. We observed the same protection in both situations: less dopamine depletion and less decrease in the number of dopaminergic cells in the substantia nigra (SN). Dexamethasone also similarly decreased the inflammatory reaction (glial activation, lymphocytic infiltration) in the injured areas. Our study showed that dexamethasone may exert a neuroprotective effect towards neurons injured by MPTP, but only when used in a proper dose. The mechanism of dexamethasone protective properties may be an inhibition of inflammatory process; however, direct interactions with neurons are also possible.
Department of Neurology, Institute of Psychiatry and Neurology, ul. Sobieskiego 1/9, 02-957 Warsaw, Poland.
Iwona
I
Kurkowska-Jastrzebska
Tomasz
T
Litwin
Ilona
I
Joniec
Agnieszka
A
Ciesielska
Adam
A
Przybyłkowski
Andrzej
A
Członkowski
Anna
A
Członkowska
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D003907:Dexamethasone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine