当前位置： SCI文献检索 > NEUROBIOLOGY OF DISEASE期刊下所有文献 > Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia.

Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia.

Abstract：

:The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brains from patients with DYT1 dystonia have revealed few abnormalities, although recent neuroimaging studies have implied the existence of microstructural defects that might not be detectable with traditional histopathological methods. The current studies took advantage of a knock-in mouse model for DYT1 dystonia to search for subtle anatomical abnormalities in the striatum, a region often implicated in studies of dystonia. Multiple abnormalities were identified using a combination of quantitative stereological measures of immunohistochemical stains for specific neuronal populations, morphometric studies of Golgi-stained neurons, and immuno-electron microscopy of synaptic connectivity. In keeping with other studies, there was no obvious loss of striatal neurons in the DYT1 mutant mice. However, interneurons immunoreactive for choline acetyltransferase or parvalbumin were larger in the mutants than in control mice. In contrast, interneurons immunoreactive for neuronal nitric oxide synthase were smaller in the mutants than in controls. Golgi histochemical studies of medium spiny projection neurons in the mutant mice revealed slightly fewer and thinner dendrites, and a corresponding loss of dendritic spines. Electron microscopic studies showed a reduction in the ratio of axo-spinous to axo-dendritic synaptic inputs from glutamatergic and dopaminergic sources in mutant mice compared with controls. These results suggest specific anatomical substrates for altered signaling in the striatum and potential correlates of the abnormalities implied by human imaging studies of DYT1 dystonia.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Song CH,Bernhard D,Bolarinwa C,Hess EJ,Smith Y,Jinnah HA

doi

10.1016/j.nbd.2013.01.008

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

362-71

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(13)00032-6

journal_volume

pub_type

杂志文章

在线工具

Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia.