Shinsuke Satoh

Inhibition of rostral basal forebrain neurons promotes wakefulness and induces FOS in orexin neurons

The present study examined whether the activities of the rostral basal forebrain neurons alter the activities of the orexin (also known as hypocretin) neurons in the tuberal part of the hypothalamus in rats. We performed microdialysis perfusion of the ventromedial portion of the rostral basal forebrain with the GABAA receptor agonist muscimol to inhibit focally the neuronal activities in the rostral basal forebrain. Then, we monitored sleep/wake behaviour and investigated the pattern of activities of orexin neurons by examining the expression of FOS as an indicator of cellular activation. Bilateral perfusion with muscimol (5, 15, and 50 µm) produced a dose‐dependent decrease in the amount of sleep. This perfusion with muscimol at 50 µm produced FOS‐like immunoreactivity in 37% of the orexin neurons located in the tuberal part of the hypothalamus, whereas the FOS‐like immunoreactivity was sparse in orexin neurons of the sleeping control rats (P = 0.001 by Mann–Whitney U‐test). Unilateral perfusion with muscimol (50 µm) also suppressed sleep. In this case, FOS‐like immunoreactivity was seen in 40% of the orexin neurons on the side ipsilateral to the perfusion site but only in 10% of orexin neurons on the contralateral side (P = 0.018 by Wilcoxon signed rank test). These functional data suggested that a sleep‐generating element in the ventromedial part of the rostral basal forebrain provides an inhibitory influence on the activities of the orexin neurons in the tuberal part of the hypothalamus.

Expression pattern of FOS in orexin neurons during sleep induced by an adenosine A2A receptor agonist

The present study examined the expression pattern of FOS in the hypothalamic peptide neurons during the sleep-dominant state induced by an adenosine A2A receptor agonist. The control rats, those that received the microdialysis-perfusion of their ventral striatum with artificial cerebrospinal fluid in the dark-active phase, spent 24% of the 90-min period prior to sacrifice in non-rapid eye movement (non-REM) sleep and 2.3% of that in REM sleep. These rats exhibited FOS, a transcription factor, in 21% of their orexin neurons and in 1.0% of their melanin-concentrating hormone (MCH) neurons in the perifornical/lateral hypothalamic areas. However, the rats perfused with 50 microM CGS21680, an adenosine A2A receptor agonist, spent 60% of the 90-min period prior to sacrifice in non-REM sleep and 11% of that in REM sleep. These rats exhibited FOS in 1.7% of their orexin neurons and FOS in 0.5% of their MCH neurons. When the sleep-dominant state was disturbed by mild stimulation and the rats were kept in the sleepy state by treatment with a sleep-inducing dose of CGS21680, the rats exhibited FOS in 13.3% of their orexin neurons, which percentage was about half of that for the control rats. These results suggest that the sleep-promoting process induced by this adenosine A2A receptor agonist was associated with a decline in the activity of orexin neurons. MCH neurons are not likely to change their activities during this sleep-promoting process.

FOS expression in orexin neurons following muscimol perfusion of preoptic area

Unilateral microdialysis-perfusion of the preoptic area with 50 μM muscimol decreased the sleep period of rats to less than 3% of the baseline value over a 90 min period before death (p = 0.018 by Wilcoxon signed-rank test). These rats showed the expression of FOS in 36% of the orexin neurons located in the perifornical/lateral hypothalamic areas on the side ipsilateral to the perfusion site, but in only 3% of the orexin neurons on the side contralateral to it (p = 0.018 by Wilcoxon signed-rank test). These results suggest that subpopulations of the preoptic neurons give an inhibitory tone to the activities of the orexin neurons in the perifornical/lateral hypothalamic areas.

A role of the C-terminus of aquaporin 4 in its membrane expression in cultured astrocytes

Background: Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, which is localized in the astrocyte plasma membrane. Membrane targeting of AQP4 is essential to perform its function. The mechanism(s) of membrane targeting is not clear in astrocytes.

905 Role of Cox-2 enzyme in the interleukin-1-induced slow-wave sleep

Li-Ping Lin, Khalil Mansur, Hiroshi Kiyama We identified that IL-2 receptor gamma chain (IL-2Rg) which is common component among IL-2 family receptors, was localized in the median eminence (ME). Following intravenous administration of IL-2. IL-4 and IL-7: c-Fos expression was dramatically induced in the parvocellular paraventricular nucleus. .?ibout 80% and 5% of these c-Fos neurons were shown to be co-localized with CRF and AVP neurons respectively. Our result suggests that these cytokines could activate CRF neurons via IL-2Rg located in ME.

1004 Sleep-promoting effect of interleukin- 1 β in the rostral basal forebrain

To investigate an inhibitory action of melanocyte stimulating hormone(MSH) to interleukin-1 ,3(IL-1,3), we examined Fos expression in paraventricular nucleus(PVN) in immunohistochemistry and nociceptive response used by hot-plate test after intracerebroventricular administration of IL-lp and MSH in rats. A microinjection of IL-lp(lOpg, lng, and lOOng/rat) in lateral cerebral ventricle induced Fos expression in PVN, especially medial parvocellular subdivision. Fos protein was expressed remarkably and increased by the administration of IL-l,3 1Opg more than other concentrations. Response latency time of paw lick using hot-plate test shortened by the microinjection of IL-18 lOpg, but did not by 100ng. Co-microinjection of MSH 30ng with IL-lp inhibited Fos expression in PVN and the shortened response time by IL-l

Promotion of sleep mediated by the A2a-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D2 in rats

lOpg.