Sleep factors

These studies are consistent with the concept of POA control of homeostasis, but are not definitive. A definitive study demonstrating the necessity of the POA for homeostatic control of sleep using the lesion method would be difficult to interpret since baseline sleep would be greatly diminished. Instead, recent studies have examined the role of the POA in response to endogenous sleep factors thought to underlie sleep homeostasis. 

A fundamental question concerns the neurochemical mechanisms that regulate the activity of POA sleep-active neurons. Currently, this problem has been approached through studies of putative sleep factors , endogenous... 

IL-ip is a well documented sleep factor (reviewed by Obal Krueger, 2003). Its administration increases sleep, its blockade decreases sleep and sleep rebound, and its transcription increases during waking. IL-1 receptor knock-out mice sleep less. Local application of IL-1 p in POA also stimulates NREM sleep. We examined the effects of local administration of IL-1 p and an antagonist through microdialytic application adjacent to lateral POA neurons (Alam et at, 2004). Neuronal activity is recorded within 0.5-1.0 mm of a microdialysis membrane in unrestrained rats. IL-ip potently inhibited the activity of 79% of wake-active neurons. The inhibitory response to IL-ip of wake-active neurons could be blocked by pre-treatment with IL-lra, an IL-ip antagonist. IL-ip application also excited some sleep-active neurons, but this response was inconsistent. 

Isolation of sleep factors from animals historical perspectives... 

The most recent attempt to purify sleep factor(s) from sleep-deprived animals started in the 1970s in Japan. A sleep-promoting substance (conveniently named SPS ) was purified from the brain stem of sleep-deprived rats (Nagasaki et al. 1974). The extract contained at least four somnogenic fractions. Subsequent analysis identified SPS-A as uridine (Iriki et al. 1983) and SPS-B as oxidized glutathione (Komoda et al. 1990). 

Orexin, NPY, and ghrelin as wake-promoting sleep factors... 

As early as in 1909, it was recognized that some chemical factor in the brain was responsible for recovery sleep. Cerebrospinal fluid (Legendre Pieron, 1911) or brain extract (Ishimori, 1909) from sleep-deprived dogs resulted in excess sleep when infused into the cerebral ventricles of recipient animals. The fact that the material was ineffective if heated or ultrafiltered pointed to a protein or peptide as sleep factor (Legendre Pieron, 1911). Later studies have... 

Despite theoretical and experimental indications that adenosine has hypno-genic effects, it was necessary, in order to postulate adenosine as a homeostatic sleep factor, to show that its concentration in vivo depends on previous wakefulness and sleep, and to explain the mechanism of its hypnogenic effect. 

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