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Biomedical subjects

P E Segall

Publications and source records attributed to P E Segall.

10 recordsLinked to original sources

Low temperature preservation and space medicine.

Cold maintenance may be an option for compromised space-borne astronauts. Contemporary aneurysm surgery can involve cooling below 20 degrees C for nearly one hour. Dogs and baboons have survived blood-substituted hypothermia for 1-3 hours. Hamsters have recovered from partial-freezing below -1 degree C, and supercooling at -5 degrees C. Laboratory frogs have survived partial-freezing from -9 degrees C, while in nature, frogs may overwinter in these states. While some invertebrates can tolerate freezing to cryogenic temperatures, no vertebrate has survived complete freezing. The following studies (hypothermia and sub-zero experiments) were conducted to explore low temperature preservation of rodents, dogs and baboons.

Animals↗

Histology and survival in age-delayed low-tryptophan-fed rats.

Diets containing tryptophan in concentrations 30 and 40 percent of those fed to controls from weaning to 24-30 months or more, can delay aging in Long-Evans female rats. Mortality among low-tryptophan-fed rats was greater in the juvenile period, but substantially less than controls at late ages. Histological biomarkers of aging were also delayed after tryptophan restriction in some organs (liver, heart, uterus, ovary, adrenal and spleen) but not in others (kidney, lung, aorta). Brain serotonin levels were low in tryptophan-deficient rats but showed remarkable capacity for rehabilitation. Effects on early and late mortality and brain levels of serotonin were proportional to the severity of the restriction.

Aging↗

Glutamic acid decarboxylase activity in discrete hypothalamic nuclei during the development of rats.

We have assessed the activity (nmol/mg protein/h) of glutamic acid decarboxylase (GAD) in discrete hypothalamic nuclei before and after sexual maturation in the developing female rat. Activity in other brain regions including the cortex, septum and caudate-putamen was also assessed. While there appears to be a general rise (approximately 30%), with age, in GAD activity, the rise is most marked, and highly significant (P less than 0.001), in the anterior portion of the hypothalamus (56%). In contrast, no significant increase of GAD activity was found in the medical basal hypothalamus.

Animals↗

Lifetime brain serotonin: regional effects of age and precursor availability.

In the rat, regional brain serotonin levels which do not change from 2-30 months of age are increased at 36 months. Corresponding catecholamine levels progressively decrease. Feeding a diet restricted in the amino acid tryptophan (the precursor of serotonin) from weaning to two years of age markedly reduces serotonin levels in all brain regions and lowers norepinephrine levels in the cerebral hemispheres. Regional activity of synthesizing (tyrosine and tryptophan hydroxylases) and catabolizing enzymes (MAO-A) does not change markedly with age or dietary manipulation except for sporadic increases in tryosine hydroxylase activity in pair-fed animals. Returning the tryptophan-deficient animals to a normal diet produces a certain degree of rehabilitation the effectiveness of which varies with the function considered: Impaired brain serotonin levels recover moderately but remain lower than controls as late as 36 months, growth is never completely compensated, and norepinephrine levels show a rebound increase.

Age Factors↗

Interrelations of dietary and hormonal effects in aging.

A model system is proposed which suggests that aging involves a genetically programmed process encoded within specific regions of the central nervous system and is characterized by a gradual ascendency of inhibitory over excitatory influences. The resulting neural suppression reduces tonic stimulation to the hypothalamus-pituitary-endocrine axis, the autonomic nervous system and the spinal cord, and promotes the secretion of inactive pituitary hormone, the involution of the somatic musculature (smooth, cardiac and striated) and the compromise of secretomotor function. Experimental observation from nutritional restriction studies which include the prolongation of the life-span and delays in reproductive and homeostatic aging, degenerative coat changes and the appearance of neoplasia, are considered from the perspective of this hypothesis.

Aging↗

Neural and endocrine development after chronic tryptophan deficiency in rats: I. Brain monoamine and pituitary responses.

Caloric restriction and tryptophan deficient diets have been shown to delay aging in the immature laboratory rat. Studies of monoamine levels in the brain of developing female rats fed on these diets show changes in serotonin but not norepinephrine or dopamine levels: in tryptophan-restricted rats serotonin levels were reduced in all brain areas studied, whereas in caloric-restricted animals serotonin levels were increased in the cerebral hemispheres only. Another group of animals, in which growth and maturation was delayed by feeding d,1-parachlorophenylalanine (PCPA) showed decreases in serotonin, norepinephrine and dopamine concentrations in all brain regions investigated. All treatments employed to arrest growth and maturation resulted in pituitary alterations manifested by gross, histological and ultrastructural changes. It is postulated that there maturation- and age-retarding treatments delay the development of the central nervous system resulting in postponed maturation of the neuroendocrine axis, with consequent hypoactivity of certain pituitary functions and a resultant delay in the onset of maturation and senescence.

Animals↗

Neural and endocrine development after chronic tryptophan deficiency in rats: II. Pituitary-thyroid axis.

Long-Evans female rats, 21 days of age, were weaned and placed on a control (Purina Rat Chow) diet, on a tryptophan deficient diet (T-) and on a diet complete in quality (Purina Rat Chow) but restricted to the daily amount consumed by the rats on the T- diet (pair-feeding). All animals were maintained on these diets for 1 and 2 months and then one group of T- rats was returned to the complete (Purina) diet and kept on this diet for several periods of time (up to 2 months). Growth was interrupted during the period of tryptophan deficiency and pair-feeding, but was restored to normal when the animals were returned to the Purina diet. In control rats, blood levels of TSH, T4 and T3 as determined by radio-immunoassay showed characteristic development patterns. In T- rats, hormonal developmental patterns were similar to those of controls after 1 month on the T- diet but levels fell significantly below control values after 2 months. On the other hand, hormonal levels of pair-fed rats were already significantly low 1 month after treatment and continued to remain low after 2 months. The decrease in thyroid function reported in these experiments as a result of severe dietary restrictions not only may explain the retardation of growth and development characteristic of nutritionally deficient animals, but also suggest some long-term interaction of nutrition and thyroid function on the aging process.

Animals↗

Age-related changes in the thermoregulatory capacity of tryptophan-deficient rats.

From a larger study seeking to develop indexes of physiological aging, the present experiment was designed 1) to test thermoregulatory capacity in the aging and old rat subjected to 3 minutes of whole-body ice water immersion, and 2) using this index of physiological age, to determine whether tryptophan deficiency from time of weaning can retard the onset of senescence. Results indicate a progressive prolongation of temperature recovery time from young to middle age to old, and tryptophan-deficient animals restored to commercial diet at middle age show the thermoregulatory capacity of young adults. The implications of tryptophan deficiency with respect to brain development, serotonin metabolism, and temperature regulation are also discussed in terms of the possibility of intervening with the aging process.

Age Factors↗

Patho-physiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging.

Long-Evans female rats three weeks, three months and 13-14 months of age were placed on tryptophan-deficient diets for periods ranging from a few months to nearly two years. Growth was interupted during the period of tryptophan-deficiency, but when the animals were returned to a complete diet, they gained weight and grew to normal size. Ability to reproduce, as indicated by litter production, was present at 17-28 months of age in rats which had been deprived of tryptophan, whereas no controls over 17 months of age produced any offspring. Other signs of delayed aging in the experimental group included, at advanced ages, greater longevity, as well as later onset in the appearance of obvious tumors, and better coat condition and hair regrowth. Many of these effects were also seen in pair-fed controls (fed a diet equal in amount to that eaten by the tryptophan-deprived rats, but with 1-tryptophan added). It is hypothesized that tryptophan deficiency delays growth, development and maturation of the central nervous system (CNS), in particular, by decreasing the levels of the neurotransmitter serotonin, for which tryptophan is the necessary precursor. In a parallel experiment, chronic treatment with d, 1-parachlorophenylalanine, an inhibitor of brain serotonin synthesis, from weaning until adulthood, also inhibited growth (body weight) and delayed sexual maturation (age of vaginal opening). These observations suggest that diets deficient in tryptophan or restricted in calories can affect maturation and aging by interfering with CNS protein synthesis, or neurotransmitter metabolism, or both.

Aging↗

Low tryptophan diets delay reproductive aging.

Newly weaned female rats fed diets severely deficient in the essential amino acid tryptophan show marked delays in reproductive aging, with conception and delivery occurring as late as 36 months. The rate of aging in these rats seems inversely related to both their early growth rates and the accessibility of brain tryptophan. The subsequent age retardation may depend on a reduction in both early cell loss and rate of brain maturation.

Animals↗