Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia

Osamu Yokota, Seishi Terada, Hideki Ishizu, Takeshi Ishihara, Hanae Nakashima, Aki Kugo, Kuniaki Tsuchiya, Kenji Ikeda, Toshiyuki Hayabara, Yuko Saito, Shigeo Murayama, Kenji Uéda, Frédéric Checler, Shigetoshi Kuroda

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Abstract

The pathophysiological basis of cognitive dysfunction, including frontotemporal dementia (FTD), in patients with amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALSD) remains unclear. On the other hand, increased expression of cyclooxygenase-2 (COX-2) in the spinal cord is thought to play a pivotal role in motor neuron degeneration in ALS. In this study, to assess the relationship between the neuronal COX-2 expression in the cerebrum, the formation of tau- and α-synuclein-negative but ubiquitin-positive neuronal inclusions (UPIs), and dementia in motor neuron disease (MND), we examined neuronal COX-2 immunoreactivity in the frontal cortex and hippocampus of patients with non-demented ALS without UPIs (n=11), ALSD with UPIs (n=6), and normal controls (n=24) using a quantitative immunohistochemical technique. Neuronal COX-2 expression in all CA1-4 in the hippocampus was significantly up-regulated in the ALSD group, and, to lesser degree but significantly, in the ALS group. Neuronal COX-2 expression in the frontal cortex was also significantly up-regulated in the ALSD group but not in the ALS group. These findings suggest that (1) the frontal cortex and hippocampus of MND are involved in the same pathogenic process associated with COX-2 induction that has been observed in spinal anterior horn cells, (2) COX-2 induction in the cerebrum is a pathogenic process that can occur even in the absence of UPI formation in MND, and (3) COX-2 expression in the cerebrum may be associated with cognitive dysfunction in MND.

Original languageEnglish
Pages (from-to)399-405
Number of pages7
JournalActa neuropathologica
Volume107
Issue number5
DOIs
Publication statusPublished - May 1 2004

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Keywords

  • Amyotrophic lateral sclerosis
  • Cyclooxygenase-2
  • Dementia
  • Frontotemporal dementia
  • Ubiquitin

ASJC Scopus subject areas

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

Cite this

Yokota, O., Terada, S., Ishizu, H., Ishihara, T., Nakashima, H., Kugo, A., Tsuchiya, K., Ikeda, K., Hayabara, T., Saito, Y., Murayama, S., Uéda, K., Checler, F., & Kuroda, S. (2004). Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia. Acta neuropathologica, 107(5), 399-405. https://doi.org/10.1007/s00401-004-0826-2