The selective vulnerability of striatopallidal neurons

Mitchell, Ian; Cooper, Alexandra; Griffiths, Mark

doi:10.1016/s0301-0082(99)00019-2

Cited by 158 publications

(109 citation statements)

References 253 publications

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“…It is not known if the accumulation of mhtt conglomerate results in cell death, or if the soluble form of the protein is the toxic form [8,9]. Dopamine, glutamate, and γ-aminobutyric acid are thought to be the most affected neurotransmitters in HD and are currently the focus of pharmacotherapy (Table 1) [10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Huntington's Disease

2014

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Section: Introductionmentioning

confidence: 99%

Treatment of Huntington's Disease

2014

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“…HIV dementia has been described as a subcortical dementia (Berger and Nath, 1997), aspects of which can include features of parkinsonism (Mirsattari et al, 1998) and dopamine dysfunction (Nath et al, 2000b). Moreover, striatal neurons are unique in their response to neurotoxic insults (Miller et al, 1999;Mitchell et al, 1999;Calabresi et al, 2000;Whetsell, Jr., 2002;Goody et al, 2003). Marginal neuronal losses are reported in the putamen of non-demented individuals with AIDS at autopsy (Everall et al, 1995), while more dramatic neuronal losses occur in the globus pallidus of nonhuman primates infected with SIV (Marcario et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons

et al. 2005

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The role of p38 and c-jun-N-terminal kinases 1/2 (JNK), members of the mitogen-activated protein kinase (MAPK) family, in mediating the toxic effects of HIV-1 Tat and gp120 were explored in primary mouse striatal neurons in vitro. Both Tat and gp120 caused significant increases in p38 and JNK MAPK phosphorylation, caspase-3 activity, neurite losses and cell death in striatal neurons. Tat-induced increases in caspase-3 activity were significantly attenuated by an inhibitor of JNK (SP600125), but not by an inhibitor of p38 (SB203580), MAPK. However, despite preventing increases in caspase-3 activity, JNK inhibition failed to avert Tat-induced neuronal losses suggesting that the reductions in caspase-3 activity were insufficient to prevent cell death caused by Tat. Alternatively, gp120-induced increases in caspase-3 activity, neurite losses and neuronal death were prevented by p38, but not JNK, MAPK inhibition. Our findings suggest that gp120 induces neuronal dysfunction and death through actions at p38 MAPK, while Tat kills neurons through actions that are independent of p38 or JNK MAPK, or through the concurrent activation of multiple proapoptotic pathways.

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“…For example, striatal atrophy and choreiform movements seen in Huntington's disease are attributed to the progressive degeneration of striatal medium spiny projection neurons (Reiner et al, 1988; Albin et al, 1990). Considerable evidence now shows that it is the enkephalin-positive striatopallidal neurons that are the most vulnerable (Albin et al, 1992;Richfield et al, 1995Richfield et al, , 2002Mitchell et al, 1999;Deng et al, 2004) while striatal aspiny interneurons are spared in this disease (Ferrante et al, 1985;Reiner et al, 1988;Cicchetti et al, 1996;Hickey and Chesselet, 2003). Excitotoxic lesions by quinolinic acid are associated with increased concentrations of SST and neuropeptide Y as a result of preferential sparing of striatal interneurons (Beal et al, 1986(Beal et al, , 1991.…”

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confidence: 99%

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

2006

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Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an indirect dopamine agonist. In the striatum, METH has been shown to cause long lasting neurotoxic damage to dopaminergic nerve terminals and recently, the degeneration and death of striatal cells. The present study was undertaken to identify the type of striatal neurons that undergo apoptosis after METH. Male mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h later. To demonstrate that METH induces apoptosis in neurons, we combined terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining with immunohistofluorescence for the neuronal marker neuron-specific nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout the striatum. METH induces apoptosis in approximately 25% of striatal neurons. Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, dorsolateral and ventrolateral quadrants of the striatum did not reveal anatomical preference. The type of striatal neuron undergoing cell death was determined by combining TUNEL with immunohistofluorescence for selective markers of striatal neurons: dopamine-and cAMP-regulated phosphoprotein, of apparent M r 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine-and cAMP-regulated phosphoprotein, of apparent M r 32,000-positive neurons (projection neurons), 45% of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of cholinergic neurons in the dorsal-medial striatum. In contrast, the SST-positive interneurons were refractory to METH-induced apoptosis. Finally, the amount of cell loss determined with Nissl staining correlated with the amount of TUNEL staining in the striatum of METH-treated animals. In conclusion, some of the striatal projection neurons and the GABAparvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH. This imbalance in the populations of striatal neurons may lead to functional abnormalities in the output and processing of neural information in this part of the brain. Keywords methamphetamine; apoptosis; striatum; projection neurons; interneurons Methamphetamine (METH) is a potent and addictive psychostimulant. The neurotoxic effects of this substituted amphetamine are associated with its ability to induce an overflow of dopamine in the synapse by displacing vesicular dopamine stores (Raiteri et al., 1979; Liang and Rutledge, 1982a,b;Schmidt et al., 1985;Sulzer et al., 1995). Displaced dopamine molecules and its metabolites can be readily oxidized to reactive quinones and semiquinones (Cadet and Brannock, 1998) and nitrogen radicals (Lipton and Rosenberg, 1994;Imam et al., 1999) that affect a wide range of modifications of proteins, sugars, and lipids. Augmented levels of dopamine in the synapse induced by METH have been shown in humans (Wilson et al., 1996;McCann et al., 1998), non-human primates (Seiden et al., 1976;Villemagne et al., 1998;Harvey e...

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The selective vulnerability of striatopallidal neurons

Cited by 158 publications

References 253 publications

Treatment of Huntington's Disease

Treatment of Huntington's Disease

Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons

Methamphetamine-induced cell death: Selective vulnerability in neuronal subpopulations of the striatum in mice

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