Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia.
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 alpha-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.
Yokota
Osamu
O
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. oyokota1@yahoo.co.jp
Terada
Seishi
S
Ishizu
Hideki
H
Ishihara
Takeshi
T
Nakashima
Hanae
H
Kugo
Aki
A
Tsuchiya
Kuniaki
K
Ikeda
Kenji
K
Hayabara
Toshiyuki
T
Saito
Yuko
Y
Murayama
Shigeo
S
Uéda
Kenji
K
Checler
Frédéric
F
Kuroda
Shigetoshi
S
D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000201:enzymology*; D002452:Cell Count / Q000379:methods; D051546:Cyclooxygenase 2; D003704:Dementia / Q000201:enzymology* / Q000209:etiology; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011180:Postmortem Changes; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D008565:Membrane Proteins; D010446:Peptide Fragments; D025801:Ubiquitin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases