Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Brain Pathol ; 21(3): 330-48, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20969653

RESUMO

Prenatal systemic inflammation has been implicated in neurological diseases, but optimal animal models have not been developed. We investigated whether a partial genetic deletion of glial cell line-derived neurotrophic factor (Gdnf(+/-)) increased vulnerability of dopamine (DA) neurons to prenatal lipopolysaccharide (LPS). LPS [0.01 mg/kg intraperitoneal (i.p.)] or saline was administered to wild-type (WT) or Gdnf(+/-) pregnant mice on gestational day 9.5. Male offspring were examined at 3 weeks, 3 and 12 months of age. There was a progressive degeneration of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) with age in Gdnf(+/-) but not in WT mice, with no observed effects on locus coeruleus (LC) noradrenergic neurons or DA neurons of the ventral tegmental area. Inflammatory markers were elevated in SN of LPS treated offspring, with exacerbation in Gdnf(+/-) mice. Intracellular accumulation of α-synuclein (α-syn) immunoreactivity in DA neurons of SN was observed in all groups of Gdnf(+/-) and in WT mice with prenatal LPS, with altered distribution between pars reticulata (pr) and pars compacta (pc). The findings suggest that prenatal LPS leads to accelerated neuropathology in the SN with age, and that a partial loss of GDNF exacerbates these effects, providing a novel model for age-related neuropathology of the nigrostriatal DA system.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Doenças Neurodegenerativas/patologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Substância Negra/imunologia , Tirosina 3-Mono-Oxigenase/metabolismo , Fatores Etários , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/imunologia , Heterozigoto , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Knockout , Neostriado/imunologia , Neostriado/metabolismo , Neostriado/patologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Gravidez , Substância Negra/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...