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

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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.

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Acknowledgements

We would like to thank Mr. M. Kobashi and Ms. M. Onbe for their excellent technical assistance. This work was supported in part by a research grant from the Zikei Institute of Psychiatry.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

    Osamu Yokota, Seishi Terada, Hideki Ishizu, Takeshi Ishihara, Hanae Nakashima, Aki Kugo & Shigetoshi Kuroda

  2. Department of Laboratory and Medicine, Matsuzawa Hospital, Tokyo, Japan

    Kuniaki Tsuchiya

  3. Department of Neuropathology, Tokyo Institute of Psychiatry, Tokyo, Japan

    Kenji Ikeda

  4. Clinical Research Institute and Department of Neurology, National Minami-Okayama Hospital, Okayama, Japan

    Toshiyuki Hayabara

  5. Department of Laboratory and Medicine, Zikei Institute of Psychiatry, Okayama, Japan

    Hideki Ishizu

  6. Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Yuko Saito & Shigeo Murayama

  7. Department of Neural Plasticity, Tokyo Institute of Psychiatry, Tokyo, Japan

    Kenji Uéda

  8. Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097, Centre National de la Recherche Scientifique, Univerisité de Nice-Sophia Antipolis, Valbonne, France

    Frédéric Checler

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  1. Osamu Yokota
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Correspondence to Osamu Yokota.

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Yokota, O., Terada, S., Ishizu, H. et al. Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia. Acta Neuropathol 107, 399–405 (2004). https://doi.org/10.1007/s00401-004-0826-2

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