Parkin-deficient rats are resistant to neurotoxicity of chronic high-dose methamphetamine

被引:4
|
作者
Sharma, Akhil [1 ]
Bazylianska, Viktoriia [1 ]
Moszczynska, Anna [1 ]
机构
[1] Wayne State Univ, Dept Pharmaceut Sci, Eugene Applebaum Coll Pharm & Hlth Sci, 259 Mack Ave, Detroit, MI 48201 USA
关键词
Methamphetamine neurotoxicity; Parkin knockout; Rats; Dopamine; Serotonin; Gliosis; Mitochondria; STRIATAL DOPAMINE; TERMINAL DEGENERATION; OXIDATIVE STRESS; NULL MICE; DISEASE; KNOCKOUT; ABNORMALITIES; GLUTATHIONE; INHIBITION; NEURONS;
D O I
10.1016/j.expneurol.2021.113811
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Methamphetamine (METH) is a highly addictive and powerful central nervous system psychostimulant with no FDA-approved pharmacotherapy. Parkin is a neuroprotective protein and its loss of function contributes to Parkinson's disease. This study used 3-month-old homozygous parkin knockout (PKO) rats to determine whether loss of parkin protein potentiates neurotoxicity of chronic METH to the nigrostriatal dopamine pathway. PKO rats were chronically treated with 10 mg/kg METH for 10 consecutive days and assessed for neurotoxicity markers in the striatum on the 5th and 10th day of withdrawal from METH. The PKO rats showed higher METHinduced hyperthermia; however, they did not display augmented deficits in dopaminergic and serotonergic neurotoxicity markers, astrocyte activation or decreased mitochondrial enzyme levels as compared to wild-type (WT) rats. Interestingly, saline-treated PKO rats had lower levels of dopamine (DA) as well as mitochondrial complex I and II levels while having increased basal levels of glial fibrillary acidic protein (GFAP), a marker of gliosis. These results indicate PKO display a certain resistance to METH neurotoxicity, possibly mediated by lowered DA levels and downregulated mitochondria.
引用
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页数:15
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