Thrombin-induced microglial activation contributes to the degeneration of nigral dopaminergic neurons in vivo / 神经科学通报·英文版
Neuroscience Bulletin
;
(6): 66-72, 2008.
Artículo
en Inglés
| WPRIM
| ID: wpr-264695
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo.</p><p><b>METHODS</b>After stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) immunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitric-oxide synthase (iNOS) expression.</p><p><b>RESULTS</b>(1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH immunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombin-injected rats was significantly higher than that of controls (P < 0.05).</p><p><b>CONCLUSION</b>Thrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Patología
/
Fisiología
/
Factores de Tiempo
/
Tirosina 3-Monooxigenasa
/
ARN Mensajero
/
Sustancia Negra
/
Inmunohistoquímica
/
Trombina
/
Dopamina
/
Regulación hacia Arriba
Límite:
Animales
Idioma:
Inglés
Revista:
Neuroscience Bulletin
Año:
2008
Tipo del documento:
Artículo
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