Pathologic involvement of glutamatergic striatal inputs from the cortices in TAR DNA-binding protein 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Yuichi Riku, Hirohisa Watanabe, Mari Yoshida, Maya Mimuro, Yasushi Iwasaki, Michihito Masuda, Shinsuke Ishigaki, Masahisa Katsuno, Gen Sobue

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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 (FTLDTDP) 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 sociocognitive declines in a disease spectrum of TDP-43 proteinopathy.

Original languageEnglish
Pages (from-to)759-768
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number9
DOIs
Publication statusPublished - 09-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Pathologic involvement of glutamatergic striatal inputs from the cortices in TAR DNA-binding protein 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this