INTRODUCTION

 

 
 
 

    The regulatory role of endogenous peptides in the control of sleep and wakefulness was first indicated by the classical studies in Japan and France at the beginning of this century. It was observed that cerebro-spinal fluid (CSF) of a sleep deprived dog promoted sleep when injected intracerebroventricularly (i.c.v.) to a recipient dog (Ishimori 1909, Legendre and Piéron 1910). A hypothesis was put forward that sleep promoting substances accumulated in CSF during wakefulness. In further studies it was found that heating or ultrafiltration abolished the observed sleep promoting effect (Legendre and Piéron 1912), suggesting that the substance was structurally a thermolabile macromolecule, possibly a peptide.

    To date several peptides have been found which affect sleep when injected systemically or directly into the brain (Borbély and Tobler 1989). However, administration of pharmacological doses of a peptide does not necessarily indicate that the peptide has an endogenous function in the regulation of sleep. In addition it is required that the secretion rhythm of the sleep promoting substance is associated with the sleep-wake rhythm. Blockade of the action of the endogenous  peptide should also have an opposite effect on sleep, and manipulation of the spontaneous sleep-wake rhythm e.g. by sleep deprivation should affect the activity of this peptide system. According to current knowledge there are three putative neuroendocrinological systems which may be associated with specific vigilance states: association of growth hormone secretion with slow wave sleep (SWS), the hypothalamo-pituitary-adrenal axis with wakefulness, and the VIP/prolactin system with REM sleep (Steiger and Holsboer 1997). In addition, there are several other neuropeptides and macromolecules which affect the structure of sleep, but their endogenous function in sleep regulation is not completely clear (Inoué and Krueger 1990).

    Secretion of GH and the amount of deep SWS decrease similarly during normal aging (Van Cauter et al. 1998). Decreased SWS may be one contributing factor to poor sleep quality and increased prevalence of sleep disorders in the elderly. Also in some pathological conditions, such as fatal familiar insomnia, the deterioration of sleep is coupled with a simultaneous decrease in GH-secretion (Portaluppi et al. 1995). It is possible that this simultaneous decrease in both GH secretion and SWS is generated by a common neural mechanism, which may be related to the GH regulatory neuropeptide system. Better knowledge about this mechanism could create new strategies for the development of more physiological methods for the management of poor sleep quality associated with normal aging and pathological conditions.
 

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