Search PubMedSearch

Biomedical subjects

J R Pappenheimer

Publications and source records attributed to J R Pappenheimer.

7 recordsLinked to original sources

"Nature's soft nurse": a sleep-promoting factor isolated from brain.

A sleep promoting factor has been extracted and purified from cerebrospinal fluid of sleep-deprived goats, from whole brains of sleep-deprived rabbits and from brainstems of slaughterhouse cattle. Intraventricular infusion of the purified material into rats, cats, rabbits or squirrel monkeys induces excess slow-wave sleep in the recipients for several hours following the infusion. The excess sleep appears similar to the deep slow-wave sleep which normally follows sleep deprivation; it is characterized by EEG slow waves of greater than normal amplitude and an increase in both the number and duration of sleep episodes. The sleep factor appears to be a small peptide of molecular weight 350--500 daltons and the effective dose is of the order of a few picomols per gram brain. A similar, perhaps identical, factor is present in human urine.

Animals

Sleep-promoting factor S: purification and properties.

Sleep-promoting factor was purified from acid/acetone extracts of whole brains of rabbits and from brainstems of slaughterhouse cattle. Intraventricular infusion of extracts purified by means of ion exchange and gel filtration induced excess slow-wave sleep in rabbits for 5-10 hr. The procedure is simple and provides material suitable for physiological studies. Further treatment by partition chromatography and electrophoresis yielded an active product that was purified at least 1 million-fold. This product was inactivated by incubation with mixed carboxypeptidases A and B. Amino acid analysis of acid hydrolysates indicated that the effective dose was less than 150 pmol per rabbit and the original concentration in brain tissue was of the order of 30 pmol/g of brain.

Animals

Sleep and respiration of rats during hypoxia.

1. The effects of hypoxia on slow-wave sleep (SWS) and of SWS on respiratory responses to hypoxia were investigated on rats provided with chronically implanted cortical electrodes. 2. During the daytime (5-7 hr periods) the proportion of time spent in SWS was 45% (S.E. +/- 1.0%) when the rats breathed air. Exposure to 10% O2 (equivalent to 18,000 ft.) reduced this proportion to 27% (S.E. +/- 2.5%). During hypoxia the intensity of e.e.g. activity in SWS (mean, rectified slow-wave voltage) rarely equalled the normal values characteristic of the same rats in fully developed SWS breathing air. The normal pattern of 5-15 min episodes of SWS was changed by hypoxia to a series of brief (2-3 min) incompletely developed episodes. 3. Addition of CO2 to inspired gas failed to prevent the reduction of SWS during hypoxia. CO2 in normal O2 did not alter sleep significantly. The effects of hypoxia on sleep therefore depend upon changes in O2 pressure rather than upon changes in CO2. 4. The effect of SWS on respiration of rats breathing air was to decrease frequency and minute volume by 10-20%. In hypoxia, however, the frequency increased markedly when the animals entered SWS ; minute volume was not significantly changed. It follows that stimulation of breathing by hypoxia is greater during SWS than during wakefulness. 5. The anomalous increase of respiratory frequency when hypoxic rats entered SWS was abolished by addition of CO2 to the hypoxic gas mixture. 6. Steady-state gaseous metabolism (Vo2 Vco2) was decreased 18 +/- 3% during hypoxia and was increased 31 +/- 4% during exposure to 5% CO2. The implications of these changes for interpretation of respiratory responses to O2 and CO2 are discussed.

Animals

Extraction of sleep-promoting factor S from cerebrospinal fluid and from brains of sleep-deprived animals.

Sleep-promoting factor (factor S) was extracted, partially purified, and concentrated from cerebrospinal fluid and from acid-acetone extracts of brain stem anc cortex of sleep-deprived goats and sheep. 2. Solutes greater than 500 daltons were largely removed by serial ultrafiltrations through molecular sieves (Amicon membranes UM10 and UM05); solutes less than 350 daltons were largely eliminated by gel filtration through Sephadex G10 columns. Sleep-promoting activity was found in a fraction eluted prior to [14C] sucrose marker. 3. Concentrated fraction were infused intraventricularly in rats (0.1 ml in 30 min just prior to 12-h dark cycle) and in rabbits (0.3 ml in 90 min in morning). Sleep-promoting activity was assayed by decrease in nocturnal locomotor activity of rats and by duration and amplitude of slow-wave cortical EEG in rabbits.

Animals