Injury and strain-dependent dopaminergic neuronal degeneration in the substantia nigra of mice after axotomy or MPTP
Identifieur interne : 000950 ( PascalFrancis/Checkpoint ); précédent : 000949; suivant : 000951Injury and strain-dependent dopaminergic neuronal degeneration in the substantia nigra of mice after axotomy or MPTP
Auteurs : LI LIU [Canada] ; Shu S. Hsu [Canada] ; Suneil K. Kalia [Canada] ; Andres M. Lozano [Canada]Source :
- Brain research [ 0006-8993 ] ; 2003.
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Abstract
We studied the effects of axotomy or neurotoxin on the survival of substantia nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6. Fluoro gold (FG) was injected into both striata of the mice to retrogradely label the nigrostriatal neuronal population. Ten days later, these neurons were axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered intraperitonealy for 2 days to produce bilateral degeneration. MFB transection or MPTP administration produced a progressive loss of FG-labeled and tyrosine hydroxylase immunolabeled (TH+) neurons in both strains. Relative to control, 72% of SNpc neurons died 4 weeks after axotomy in C57BL/6 mice and 50% died after axotomy in FVB/N mice. MPTP resulted in death of 80% of SNpc neurons in C57BL/6 mice but only 40% in the FVB strain 4 weeks after MPTP administration. In this more sensitive strain, MPTP cell death was associated with positive staining for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and nuclear condensation. In contrast, no TUNEL staining was detected in SNpc after MPTP in FVB/N mice. Further, while similar kinetics and extent of cell death accompanied axotomy, axotomy-induced cell death was TUNEL negative in both FVB/N and C57BL/6 mice, Double staining for TUNEL and microtubule associated protein 2 confirmed that the majority of the TUNEL positive cells were neurons. These data indicate that genetic factors and the type of lesion play an important role in determining death of dopaminergic neurons after injury.
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Hsu</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, University of Toronto, 399 Bathurst Street</s1><s2>Toronto ON, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto ON, M5T 2S8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kalia, Suneil K" sort="Kalia, Suneil K" uniqKey="Kalia S" first="Suneil K." last="Kalia">Suneil K. Kalia</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, University of Toronto, 399 Bathurst Street</s1><s2>Toronto ON, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto ON, M5T 2S8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, University of Toronto, 399 Bathurst Street</s1><s2>Toronto ON, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Toronto ON, M5T 2S8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Brain research</title><title level="j" type="abbreviated">Brain res.</title><idno type="ISSN">0006-8993</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain research</title><title level="j" type="abbreviated">Brain res.</title><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Axotomy</term><term>Cell death</term><term>Degeneration</term><term>Dopaminergic neuron</term><term>Locus niger</term><term>Mouse</term><term>Neurotoxin</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dégénérescence</term><term>Locus niger</term><term>Axotomie</term><term>Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro)</term><term>Neurotoxine</term><term>Neurone dopaminergique</term><term>Mort cellulaire</term><term>Parkinson maladie</term><term>Animal</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We studied the effects of axotomy or neurotoxin on the survival of substantia nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6. Fluoro gold (FG) was injected into both striata of the mice to retrogradely label the nigrostriatal neuronal population. Ten days later, these neurons were axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered intraperitonealy for 2 days to produce bilateral degeneration. MFB transection or MPTP administration produced a progressive loss of FG-labeled and tyrosine hydroxylase immunolabeled (TH+) neurons in both strains. Relative to control, 72% of SNpc neurons died 4 weeks after axotomy in C57BL/6 mice and 50% died after axotomy in FVB/N mice. MPTP resulted in death of 80% of SNpc neurons in C57BL/6 mice but only 40% in the FVB strain 4 weeks after MPTP administration. In this more sensitive strain, MPTP cell death was associated with positive staining for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and nuclear condensation. In contrast, no TUNEL staining was detected in SNpc after MPTP in FVB/N mice. Further, while similar kinetics and extent of cell death accompanied axotomy, axotomy-induced cell death was TUNEL negative in both FVB/N and C57BL/6 mice, Double staining for TUNEL and microtubule associated protein 2 confirmed that the majority of the TUNEL positive cells were neurons. These data indicate that genetic factors and the type of lesion play an important role in determining death of dopaminergic neurons after injury.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0006-8993</s0></fA01><fA02 i1="01"><s0>BRREAP</s0></fA02><fA03 i2="1"><s0>Brain res.</s0></fA03><fA05><s2>994</s2></fA05><fA06><s2>2</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Injury and strain-dependent dopaminergic neuronal degeneration in the substantia nigra of mice after axotomy or MPTP</s1></fA08><fA11 i1="01" i2="1"><s1>LI LIU</s1></fA11><fA11 i1="02" i2="1"><s1>HSU (Shu S.)</s1></fA11><fA11 i1="03" i2="1"><s1>KALIA (Suneil K.)</s1></fA11><fA11 i1="04" i2="1"><s1>LOZANO (Andres M.)</s1></fA11><fA14 i1="01"><s1>Division of Applied and Interventional Research, Toronto Western Hospital Research Institute, University of Toronto, 399 Bathurst Street</s1><s2>Toronto ON, M5T 2S8</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></fA14><fA20><s1>243-252</s1></fA20><fA21><s1>2003</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>12895</s2><s5>354000116096260120</s5></fA43><fA44><s0>0000</s0><s1>© 2004 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>42 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>04-0115606</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Brain research</s0></fA64><fA66 i1="01"><s0>NLD</s0></fA66><fC01 i1="01" l="ENG"><s0>We studied the effects of axotomy or neurotoxin on the survival of substantia nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6. Fluoro gold (FG) was injected into both striata of the mice to retrogradely label the nigrostriatal neuronal population. Ten days later, these neurons were axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered intraperitonealy for 2 days to produce bilateral degeneration. MFB transection or MPTP administration produced a progressive loss of FG-labeled and tyrosine hydroxylase immunolabeled (TH+) neurons in both strains. Relative to control, 72% of SNpc neurons died 4 weeks after axotomy in C57BL/6 mice and 50% died after axotomy in FVB/N mice. MPTP resulted in death of 80% of SNpc neurons in C57BL/6 mice but only 40% in the FVB strain 4 weeks after MPTP administration. In this more sensitive strain, MPTP cell death was associated with positive staining for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and nuclear condensation. In contrast, no TUNEL staining was detected in SNpc after MPTP in FVB/N mice. Further, while similar kinetics and extent of cell death accompanied axotomy, axotomy-induced cell death was TUNEL negative in both FVB/N and C57BL/6 mice, Double staining for TUNEL and microtubule associated protein 2 confirmed that the majority of the TUNEL positive cells were neurons. These data indicate that genetic factors and the type of lesion play an important role in determining death of dopaminergic neurons after injury.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Dégénérescence</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Degeneration</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Degeneración</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Locus niger</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Locus niger</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Locus níger</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Axotomie</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Axotomy</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Axotomía</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Pyridine(1-méthyl-4-phényl-1,2,3,6-tétrahydro)</s0><s2>NK</s2><s2>FX</s2><s5>04</s5><s6>Pyridine(«1»-méthyl-«4»-phényl-«1,2,3,6»-tétrahydro)</s6></fC03><fC03 i1="05" 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sortKey="Hsu, Shu S" sort="Hsu, Shu S" uniqKey="Hsu S" first="Shu S." last="Hsu">Shu S. 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