Neuron-selective changes in RNA transcripts related to energy metabolism in toxic models of parkinsonism in rodents.
Neurobiol Dis
; 38(3): 476-81, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20307667
ABSTRACT
Dopamine (DA) neurons in the substantia nigra (SNDA neurons) are among the most severely affected in Parkinson's disease (PD). Mitochondrial complex I inhibition by rotenone or MPTP can induce SNDA neurodegeneration and recapitulate motor disability in rodents. We performed a transcriptional analysis of the midbrain response to complex I inhibition focused on selected metabolic transcripts using quantitative real-time RT-PCR in conjunction with laser-capture microdissection (LCM) of immunofluorescently targeted SNDA and ventral tegmental area (VTA) DA neurons. There were DA neuron-selective alterations in metabolic transcripts in response to generalized complex I inhibition dependent on the behavioral response of the animal, and vulnerable SNDA neurons were more dynamic in their metabolic transcriptional response than less vulnerable VTADA neurons. The metabolic transcriptional response of DA neurons may contribute significantly to the ultimate toxicity associated with mitochondrial inhibition, and better understanding of this response may provide insight into potential targets for neuroprotection in PD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Substância Negra
/
Dopamina
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Área Tegmentar Ventral
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Transtornos Parkinsonianos
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2010
Tipo de documento:
Article