Vascular Theory of Sleep
Italian physiologist A. Mosso proposed historically the first scientific concept regarding the mechanisms of sleep. Its central postulate states that falling asleep is a consequence of cerebral anemia (decreased blood flow).
To test this hypothesis, the researcher used a specially designed balance platform ("Mosso's human circulation balance"). The participant was placed on a carefully balanced bed. As the individual fell asleep, the foot end of the bed tilted downward while the head end rose upward, demonstrating a redistribution of blood flow toward the lower extremities.
Despite the validity of the observed hemodynamic changes, the scientific community deemed the theory inconclusive. Critics pointed out the impossibility of establishing a direct cause-and-effect relationship: whether cerebral blood redistribution is the physiological cause of sleep or merely a vegetative consequence of it.
Humoral Theory: The Concept of Hypnotoxins
In the 1920s, Belgian researchers Legendre and Piéron proposed a humoral model. In their view, prolonged wakefulness causes specific substances—hypnotoxins (or kenotoxins)—to accumulate in the blood, provoking sleep onset.
As experimental proof, a dog was forcibly deprived of sleep by continuous walking on a treadmill for 24 hours. Blood from the sleep-deprived animal was then transfused into a well-rested, awake recipient dog, causing it to fall asleep immediately.
This concept also faced significant criticism:
- Stress factor. The animal on the treadmill experienced severe physical exertion. Transfused active agents were likely metabolic products of muscle fatigue or stress hormones rather than specific sleep regulators.
- Conjoined twins phenomenon. Observations of conjoined twins sharing a common circulatory system demonstrated that the children could maintain independent sleep-wake cycles (one twin sleeping while the other remained awake). Consequently, peripheral blood humoral factors cannot be considered the sole trigger for sleep onset.
Neurochemical Factors of the Brain and Cerebrospinal Fluid
Modern physiology has refined the humoral theory by shifting the focus to neurochemical processes occurring within the central nervous system (CNS).
American researcher J. Pappenheimer demonstrated the central localization of sleep factors. He deprived goats of sleep for 48 hours and subsequently sampled their cerebrospinal fluid (CSF). Infusing this CSF into the cerebral ventricles of awake cats induced immediate sleep. This confirmed that the sleep-promoting factor (referred to in literature as "Factor S") is produced and acts primarily within the CSF and brain structures.
Delta-Sleep-Inducing Peptide and Other Regulators
Researcher M. Monnier experimentally induced sleep in rabbits using low-frequency electrical stimulation of the anterior hypothalamus. From the thalamic and hypothalamic tissues of these animals, a specific nonapeptide consisting of 9 amino acids (Tyr-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) was isolated.
Administering this compound to awake animals produced slow, high-amplitude delta waves on the electroencephalogram (EEG). The substance was named delta-sleep-inducing peptide (DSIP). This discovery stimulated further search for endogenous central sleep regulators.
In addition, several other biologically active substances modulate the sleep-wake cycle:
- Increase sleep duration: Interleukin-1 (IL-1), prostaglandin $D_2$.
- Inhibit sleep onset: Prostaglandin $E_2$, $\alpha$-melanocyte-stimulating hormone ($\alpha$-MSH).