RESUMO
We analyzed smooth muscle actin (SMA) immunoreactivity in brain blood vessels of 10 ApoE 4,4 Alzheimer disease (AD) patients and 10 ApoE 3,3 AD patients matched for age, sex, and duration of dementia. We also examined 10 cognitively and neuropathologically normal controls matched for age and sex. Vascular SMA immunoreactivity in the arachnoid, grey matter, and white matter was quantified by image analysis. There was less SMA immunoreactivity in blood vessels of all AD patients when compared to cognitively and neuropathologically normal controls (p < 0.001). In addition, arachnoidal vessels of ApoE 4,4 AD patients had less SMA immunoreactivity than ApoE 3,3 AD patients (p < 0.05). There is decreased vascular SMA density in arachnoid, grey matter, and white matter blood vessels in patients with AD when compared to age matched, cognitively and neuropathologically normal controls. The severity of the loss of SMA within the AD group may depend on ApoE type.
Assuntos
Actinas/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/irrigação sanguínea , Artérias Cerebrais/metabolismo , Músculo Liso Vascular/metabolismo , Actinas/deficiência , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Apolipoproteína E3 , Apolipoproteína E4 , Apolipoproteínas E/genética , Aracnoide-Máter/irrigação sanguínea , Aracnoide-Máter/patologia , Aracnoide-Máter/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Regulação para Baixo/fisiologia , Feminino , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Valores de ReferênciaRESUMO
Gonadal steroids exert an important regulatory influence upon the biosynthetic and secretory activity of the somatostatin and growth hormone-releasing hormone (GHRH) neurons controlling the release of growth hormone. It is hypothesized that some of these effects occur in an indirect transsynaptic manner through the steroid regulation of GAGAergic inputs to these cells. Using GABA(A) receptor gamma(2) subunit knockout mice (gamma(2)(-/-)), which exhibit marked deficiencies in GABA(A) receptor functioning, we have examined here whether signaling through the GABA(A) receptor has any role in maintaining normal levels of somatostatin and GHRH mRNA expression in vivo. In situ hybridization experiments using (35)S-labeled oligonucleotide probes revealed that cellular levels of somatostatin mRNA in the periventricular nucleus were significantly (p < 0.01) reduced by 16% in newborn gamma(2)(-/-) mice compared with wild-type litter mates (gamma(2)(+/+)). Somatostatin mRNA expression in the striatum was not changed. Cellular levels of GHRH mRNA expression in the arcuate nucleus were significantly (p < 0.05) reduced by 30% in gamma(2)(-/-) compared with gamma(2)(+/+) mice. These results demonstrate that deletion of the gamma(2) subunit of the GABA(A) receptor reduces somatostatin and GHRH mRNA expression within the hypothalamopituitary axis and indicate that GABA exerts a tonic stimulatory influence upon both somatostatin and GHRH biosynthesis in vivo in the neonatal mouse.