RICERCA ITALIANA     

The relationship between sleep and body adaptive responses to modifications in the internal and external environment.

Università degli Studi di Bologna

Abstract

The project will consider the mechanisms determining at a cellular and systemic level the adaptive responses of the body to changes in the internal and external environment during sleep. In particular, the study will consider from a neurochemical, neuroanatomical and neurophysiological perspective the following structures: cerebral cortex, hypothalamus, and brainstem. The systemic regulation of circulation, respiration and water and salt balance will be studied.

Principal Investigator

Carlo FRANZINI Università degli Studi di BOLOGNA

Research Objectives

The sleep cycle in mammals (Non-Rapid-Eye-Movement sleep, NREM sleep, characterized by absence of rapid eye movements, synchronized electroencephalogram, and fully effective homeostatic regulations; Rapid-Eye-Movement sleep, REM sleep, characterized by presence of rapid eye movements, desynchronized electroencephalogram, and impairment of homeostatic regulations) is the expression of a global behavior involving therefore both somatic and autonomic activity. The research project aims at studying the relationship between sleep and body adaptive responses to modifications in the internal and external environment. Both the effect of different stimulations on the sleep cycle and the effect of the sleep state on body adaptive responses will be studied. To this end, the different but complementary expertise of sleep researchers of the Universities of Bologna and Milan has been joined to present an integrated proposal approaching issues of the sleep-wake cycle. The study will consider: a) the relationship between sleep and water-salt balance, assessing the regulation of vasopressin secretion following an hyperosmotic challenge; b) the relationship between sleep and cardiovascular regulation following acoustic and hypoxic challenges; c) the relationship between sleep and the immune system following Interleukin-1 microinjections; d) electroencephalographic changes following transcranial magnetic stimulation during sleep.

First Results

a) Sleep and the regulation of water-salt balance. Phase 1: vasopressin release following hyperosmotic stimulation. A reduced or absent release of vasopressin during REM sleep with respect to NREM sleep or wakefulness will stand for a generalized impairment of hypothalamic structures in REM sleep.
b) Sleep and perturbations in cardiovascular regulation. Phase 1: experiments performed in control conditions and after acoustic and hypoxic stimulation in normotensive rats. The acoustic and hypoxic stimulation in normotensive rats should entail a reduction in sleep quality assessed on the basis of EEG, EMG, and cardiorespiratory changes. Moreover, cardiovascular and respiratory changes, secondary to the experimental challenge, may show a dependence from the sleep-wake state. Finally, this will allow to assess the sleep-state dependent cardiorespiratory risk in pathophysiological conditions.
c) Changes in the sleep-wake cycle following an immunological challenge. Phase 1: technical refinement of the stereotaxic approach, of the patch clamp recordings and of the immunohistochemical characterization. The precise determination of the stereotaxic coordinates for the placement of the cannula needed for IL-1 microinjections in vivo and the direct administration of IL-1 to cholinergic neurons of the pontine tegmentum will be performed. An inhibition of bioelectric activity would favor the hypothesis that the effect of IL-1 on REM sleep may result from an inhibition of >>>

Timescale

24 months

National and international background

In mammals, the mode of operation of regulatory mechanisms depends on the sleep-wake states (Parmeggiani, 1980); in particular, during REM sleep, autonomic regulations are significantly impaired. As a consequence: a) changes in the internal or external environments may affect the sleep-wake cycle organization; and b) the adaptive responses following environmental changes may depend on the sleep state. The project aims at studying four representative aspects of the interaction between hypnic and homeostatic regulation.
The first Research Unit will test the relationship between behavioral states and the regulation of salt and water content in body fluids, in particular that of water balance (osmoregulation). Osmoregulation is sustained by the neurohypophyseal reflex release of vasopressin, synthesized in the magnocellular hypothalamic neurons located in the supraoptic and paraventricular nuclei, induced by changes in the osmolality of body fluids. Thus, osmoregulation represents a homeostatic function under a clear hypothalamic control, but which is phylogenetically older than thermoregulation, whose impairment during REM sleep was first shown (Parmeggiani, 1980) as evidence of an homeostatic failure in this state.
The second Research Unit will consider cardiovascular changes during sleep. Peripheral (baroreflex) and central (non-baroreflex) influences converge at the level of HP regulation. The analysis of Heart Period (HP) vs. Arterial Pressure (AP >>>