Pathologic Involvement of Glutamatergic Striatal Inputs From the Cortices in TAR DNA-Binding Protein 43 kDa-Related Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis.
J Neuropathol Exp Neurol
; 76(9): 759-768, 2017 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-28859339
In frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), recent studies have presumed relationships between cognitive declines and striatal dysfunctions. The striatum contributes to socio-cognitive functions by receiving glutamatergic inputs from the cerebral cortices. However, the vulnerability of these cortico-striatal inputs is unclear in these diseases. This study aimed to evaluate the glutamatergic inputs to the striatum from the cerebral cortices in patients with sporadic TDP-43-related FTLD (FTLD-TDP) and ALS (ALS-TDP). We examined 46 consecutively autopsied patients (31 FTLD-TDP and 15 ALS patients) and 10 normal controls. The axon terminals of the glutamatergic cortico-striatal projection neurons were quantified at the striatum using antivesicular glutamate transporter-1 (VGLUT-1) immunohistochemistry. In results, all FTLD-TDP patients displayed marked depletion of VGLUT-1-positive axon terminals in the caudate head and putamen. Particularly, the patients with type C pathology showed a severe loss. The nondemented ALS patients displayed loss of VGLUT-1-positive axon terminals in the putamen, but those were relatively spared in the caudate head. Confocal microscopy revealed TDP-43 aggregations within VGLUT-1-positive axon terminals in a subset of the patients. Our results indicate marked involvement of glutamatergic striatal inputs from the cerebral cortices in association with socio-cognitive declines in a disease spectrum of TDP-43 proteinopathy.
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Vias Aferentes
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Córtex Cerebral
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Ácido Glutâmico
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Corpo Estriado
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Degeneração Lobar Frontotemporal
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Esclerose Lateral Amiotrófica
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article