Up-regulated neuronal COX-2 expression after cortical spreading depression is involved in non-REM sleep induction in rats.
Cortical spreading depression is an excitatory wave of depolarization spreading throughout cerebral cortex at a rate of 2-5 mm/min and has been implicated in various neurological disorders, such as epilepsy, migraine aura, and trauma. Although sleepiness or sleep is often induced by these neurological disorders, the cellular and molecular mechanism has remained unclear. To investigate whether and how the sleep-wake behavior is altered by such aberrant brain activity, we induced cortical spreading depression in freely moving rats, monitoring REM and non-REM (NREM) sleep and sleep-associated changes in cyclooxygenase (COX)-2 and prostaglandins (PGs). In such a model for aberrant neuronal excitation in the cerebral cortex, the amount of NREM sleep, but not of REM sleep, increased subsequently for several hours, with an up-regulated expression of COX-2 in cortical neurons and considerable production of PGs. A specific inhibitor of COX-2 completely arrested the increase in NREM sleep. These results indicate that up-regulated neuronal COX-2 would be involved in aberrant brain excitation-induced NREM sleep via production of PGs.
Cui
Yilong
Y
Molecular Imaging Research Program, Institute of Physical and Chemical Research (RIKEN), Kobe, Hyogo, Japan.
Kataoka
Yosky
Y
Inui
Takashi
T
Mochizuki
Takatoshi
T
Onoe
Hirotaka
H
Matsumura
Kiyoshi
K
Urade
Yoshihiro
Y
Yamada
Hisao
H
Watanabe
Yasuyoshi
Y
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004569:Electroencephalography; D004576:Electromyography; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012890:Sleep / Q000502:physiology*; D015854:Up-Regulation
D011453:Prostaglandins; D051546:Cyclooxygenase 2