Assuntos
Eletroacupuntura , Perda Auditiva/terapia , Receptor de Fator de Crescimento Neural/genética , Animais , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Perda Auditiva/genética , Perda Auditiva/metabolismo , Humanos , Camundongos , Camundongos Knockout , Receptor de Fator de Crescimento Neural/deficiênciaRESUMO
Disrupted-in-schizophrenia 1 (DISC1)-binding zinc finger protein (DBZ) is a DISC1-interacting molecule and the interaction between DBZ and DISC1 is involved in neurite outgrowth in vitro. DBZ is highly expressed in brain, especially in the cortex. However, the physiological roles of DBZ in vivo have not been clarified. Here, we show that development of basket cells, a morphologically defined class of parvalbumin (PV)-containing interneurons, is disturbed in DBZ knockout (KO) mice. DBZ mRNA was highly expressed in the ventral area of the subventricular zone of the medial ganglionic eminence, where PV-containing cortical interneurons were generated, at embryonic 14.5 days (E14.5). Although the expression level for PV and the number of PV-containing interneurons were not altered in the cortices of DBZ KO mice, basket cells were less branched and had shorter processes in the somatosensory cortices of DBZ KO mice compared with those in the cortices of WT mice. Furthermore, in the somatosensory cortices of DBZ KO mice, the level of mRNAs for the gamma-aminobutyric acid-synthesizing enzymes GAD67 was decreased. These findings show that DBZ is involved in the morphogenesis of basket cells.
Assuntos
Proteínas de Transporte/metabolismo , Interneurônios/patologia , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/fisiologia , Córtex Somatossensorial/patologia , Animais , Glutamato Descarboxilase/biossíntese , Imuno-Histoquímica , Hibridização In Situ , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microscopia Confocal , Proteínas do Tecido Nervoso/deficiênciaAssuntos
Alopecia em Áreas/terapia , Eletroacupuntura , Folículo Piloso/imunologia , Inflamação/prevenção & controle , Mastócitos/imunologia , Alopecia em Áreas/imunologia , Alopecia em Áreas/patologia , Animais , Anti-Inflamatórios , Doenças Autoimunes/terapia , Degranulação Celular , Modelos Animais de Doenças , Feminino , Inflamação/etiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos EndogâmicosRESUMO
BACKGROUND: Atrial fibrillation (AF) often occurs in Brugada syndrome (BrS), and BrS patients with spontaneous AF often experience ventricular fibrillation (VF) attacks. Atrial vulnerability providing a substrate for AF is known to be enhanced in BrS, but there are no data on atrial structural attributes. OBJECTIVE: The objective of this study was to assess atrial electrophysiological and structural characteristics in BrS and their relationships with gene mutations. METHODS: We studied 57 patients with BrS. Intra-atrial conduction time (CT) was defined as the interval from the stimulus at the high right atrium to atrial deflection at the distal portion of the coronary sinus. Left atrial volume index (LAVI) was measured by the modified Simpson method at left ventricular end-systole using echocardiography. SCN5A mutations were analyzed in all patients. RESULTS: In patients with documented VF, spontaneous AF frequently occurred and prolonged CT and increased LAVI were observed compared with those in patients without VF (all P < .05; LAVI: 22 +/- 5 vs. 32 +/- 7 ml/m(2)). Even among patients without AF, CT and LAVI were still increased in patients with VF (all P < .05; LAVI: 22 +/- 5 vs. 29 +/- 5 ml/m(2)). The presence of SCN5A mutation was associated with prolonged CT (P < .05) and increased LAVI (P < .01), but not with arrhythmic episodes. CONCLUSION: Both atrial vulnerability and structural remodeling are enhanced in high-risk patients with BrS, even in those without AF. These morphological characteristics suggest that BrS is a form of genetic myocardial disease.
Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Síndrome de Brugada/diagnóstico por imagem , Síndrome de Brugada/fisiopatologia , Ecocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas , Fibrilação Atrial/genética , Síndrome de Brugada/genética , Distribuição de Qui-Quadrado , Desfibriladores Implantáveis , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Canal de Sódio Disparado por Voltagem NAV1.5 , Canais de Sódio/genéticaRESUMO
The neurotrophin receptor p75 (p75NTR) is expressed in the developmental stage of the cochlea. However, the role of the p75NTR in the inner ear remains to be established. In this study, we conducted electrophysiological and morphological analyses of the auditory function of mice carrying a mutation in the p75 gene at different longitudinal stages. The mice carrying a mutation in the p75 gene showed an age-related progressive hearing loss. At 1 month, there was no obvious morphological change in the cochlea of the mice carrying a mutation in the p75 gene compared to wild-type mice, except for a slight loss of spiral ganglion neurons (SGNs). Auditory function was not significantly different between both genotypes from 1 to up to 4 months of age. The mice carrying a mutation in the p75 gene started to show progressive hearing loss at 4 months, when both SGN degeneration and hair cell (HC) loss were observed at the basal turn. These results suggest that the neurotrophin receptor p75 may play a significant role in the maintenance of cochlear function, and that mice carrying a mutation in the p75 gene could be a good animal model of early onset progressive hearing loss.