Neurochemical and molecular mechanisms of sleep

Yuri F. Pastukhov

Sechenov Institute of evolutionary physiology and biochemistry, RAS, St.-Petersburg, Russia e-mail: pastukh@iephb.ru

 

Нейрохимические и молекулярные механизмы сна

Ю.Ф. Пастухов

Институт эволюционной физиологии и биохимии им. И.М.Сеченова, РАН,

Санкт-Петербург, Россия

 

 

Sleep is a necessary component of biorhythmic regulation of tachymetabolism and homeostasis in mammals and birds, but its peculiarities in different ecological groups and some species depend on the accordance with other important biological functions supporting survival of species. [Pastukhov et al., 2001- 2003].

During the alternation of sleep-wakefulness states the organization and interaction of a great number of physiological processes changes [Rechtschaffen, 1998]. Multifactorial regulation these processes implies the absence of a single factor specific for sleep. For example, the regulation of Non REM sleep may involve inhibitory mediators, “sleep factors”, hormones, peptides, cytokines, prostaglandins, neuromodulators [Obal, Krüger, 2003]. The “choice” of the “dynamic cocktail” participators from sleep-promoting substances is appeared to be consistent with current biological needs.

The first steps in identifying of the molecular mechanisms of sleep states multifactorial regulation have been taken. It was demonstrated that stress response genes such as heat shock protein 70 and 83 kDa (hsp70, Hsp83) protect against lethal effects of “sleep” (rest) deprivation in Drosophila [Shaw et al., 2002]. Hsc70, Hsp70 and Hsp40 were found to be localized to the glial cells, neurons and pre- and post-synaptic elements in mammalian central nervous system, indicating a regulating and neuroprotective synaptic role for these HSPs [Bechtold et al., 2000]. HSPs as molecular chaperones, especially Hsp70, are able to inhibit the aggregation of partially denatured proteins and refold them. Hsp70 protect the brain from environmental, genotoxic and proteotoxic stresses, and severe ischemia [Giffard et al., 2004; Guzhova, 2005]. Microinjections of exogenous Hsp70 into the third ventricle induce a pronounced increase in the total time of Non REM sleep and a decrease in brain temperature and contractile muscle activity in non-stress conditions as well as following moderate and severe stress, which indicates an enhancement in anti-stress function of Non REM sleep. [Pastukhov et al., 2004, 2005]. Hsp 70 normalizes visceral components of paradoxical sleep during excitement of cholinergic receptors of the N. reticularis pontis oralis [Guselnikova et al., 2003, 2005] and decreases the severity of seizure convulsions during superfluous activation of central NMDA glutamate receptors [Pastukhov et al., 2005]. It is suggested that Hsp70 and other molecular substances having neuroprotective properties may manifest sleep-promoting activity. The work is supported by RFRF (grant 03-33024).

 

 

Сведение об авторе

Пастухов Юрий Федотович

Институт эволюционной физиологии и биохимии им. И.М. Сеченова, РАН

Зав. лабораторий сравнительной термофизиологии, д.б.н. акад. РАЕН.

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