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.
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
SPOKAS, EG
SULEYMANOV, OD
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
SULEYMANOV, OD
BITTNER, SE
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
BITTNER, SE
CAMPION, JG
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
CAMPION, JG
GORCZYNSKI, RJ
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
GORCZYNSKI, RJ
LENAERS, A
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
LENAERS, A
WALSH, GM
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CONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUMCONTINENTAL PHARMA INC, PARC SCI DELOUVAIN LA NEUVE, B-1348 MONT ST GUIBERT, BELGIUM
机构:
Univ Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Tomenendalova, J.
Mayer, J.
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Fac Hosp Brno, Dept Internal Med Hematoncol, Brno, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Mayer, J.
Doubek, M.
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Fac Hosp Brno, Dept Internal Med Hematoncol, Brno, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Doubek, M.
Scheer, P.
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Univ Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Scheer, P.
Horky, D.
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Univ Vet & Pharmaceut Sci, Cent Clin Lab, Fac Vet Med, Brno, Czech Republic
Masaryk Univ, Dept Histol & Embryol, Brno, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Horky, D.
Rehakova, K.
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机构:Univ Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic
Rehakova, K.
Doubek, J.
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Univ Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech RepublicUniv Vet & Pharmaceut Sci, Dept Physiol, Fac Vet Med, Brno 61242, Czech Republic