Search PubMed⌕ Search

Biomedical subjects

A Brodish

Publications and source records attributed to A Brodish.

At least 19 recordsLinked to original sources
PubMed1991

Decreased plasticity of glucoregulatory responses in aged rats: effects of chronic stress.

These experiments were conducted to determine the effects of age and chronic stress on the ability of rats to attenuate stimulus-induced glucose and insulin responses during repeated exposure to a mild stressor. Young (5-month) and old (21-month) Fischer 344 male rats were either exposed to intermittent sessions of an escapable footshock stress for 3 months, or to no chronic stress. Afterwards, blood samples were obtained from each rat before, during, and after the first and fourth exposure to a novel motion stimulus. Between the first and the fourth exposure to the motion stimulus a pronounced attenuation of glucose and insulin responses was seen in both groups of young rats, and in old chronically stressed rats, but not in old control animals. Thus, it appears that the adverse effects of aging on plasticity of glucoregulatory response processes were significantly diminished by exposure of the animals to periodic challenges from their external environment.

Acute Disease↗
PubMed1991

Chronic stress-induced acceleration of electrophysiologic and morphometric biomarkers of hippocampal aging.

There is increasing evidence that experimental interventions that alter adrenal corticosteroid plasma concentrations can modulate aging changes in the rodent hippocampus. However, there still is very little evidence that elevation of endogenous corticosteroid levels within physiological ranges, such as occurs during chronic stress, can accelerate hippocampal aging-like changes. In addition, almost all prior intervention studies of corticosteroid effects on brain biomarkers of aging have utilized morphologic measures of aging, and it is not yet clear whether electrophysiologic biomarkers of hippocampal aging can also be accelerated by conditions that elevate corticosteroids. In the present studies, specific pathogen-free rats of three ages (4, 12, and 18 months at the start) were trained for 6 months (4 hr/d, 5 d/week) in a two-way shuttle escape task, using low intensity foot shock. This task induces "anxiety" stress, because animals receive little actual shock, but chronic training in the task has been shown to elevate plasma corticosteroids and to downregulate hippocampal corticosteroid receptors. At the end of 6 months, animals were allowed to recover for 3 weeks and were then assessed in acute, anesthetized preparations on a battery of hippocampal neurophysiological markers known to separate young from aged animals (frequency potentiation, synaptic excitability thresholds, EPSP amplitude). The brains were then fixed and sectioned for quantification of neuronal density in field CA1 (a highly consistent anatomic marker of hippocampal aging). The pattern of stress effects differed considerably across age groups. The two younger stress groups exhibited increased evidence of aging-like neurophysiologic change, but exhibited no indications of accelerated neuronal loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Scleral calcification and photoreceptor cell death during aging and exposure to chronic stress.

Male and female Fischer 344 rats of three different ages (12, 18, and 25 months) have been examined for the presence of photoreceptor (PR) cell loss and for occurrence of scleral cartilage and bone formation. In addition, male and female rats, aged 11 months at the beginning of the experiments, were exposed to chronic stress for either 0.5, 2, 4, or 6 months. Photoreceptor cell death gradually increases during the aging process and is exacerbated by exposure to chronic stress. It is more severe in the peripheral than the central retina and exposure to stress increases this pattern of cell loss. The superior retina is more severely affected than the inferior hemisphere in aging and during stress. The incidence of scleral cartilage or bone formation increases with age in male and female rats, but with stress exposure an increase is seen in males only. Bone formations occur more frequently in male than in female animals and are almost always (97%) located in the superior hemisphere of the eye. Although there appears to be a direct relationship between photoreceptor cell death and the occurrence of scleral ossifications in group data, in individual eyes the bone formations are not always associated with severity of PR cell loss. The relationship of PR cell death and incidence of scleral ossification to gender and to exposure to stress supports a hypothesis for an endocrine basis of ocular aging.

Aging↗
PubMed1990

Central but not peripheral opiate receptor blockade prolonged pituitary-adrenal responses to stress.

Evidence from pharmacological studies suggest that opiate systems may serve either inhibitory or stimulatory functions on stress-induced responses of the hypothalamic-pituitary-adrenocortical (HPA) axis. The objective of these experiments was to determine whether these discrepant findings may result, in part, from differential effects of central or peripheral opiate receptor blockade on HPA axis responses. To this effect, groups of rats received injections of either saline, naltrexone (NHCl) or the quaternary analogue naltrexone methobromide (NMBr). The animals were then exposed to 30 min of a motion stressor and blood samples were obtained from each rat for analysis of ACTH, corticosterone, and prolactin. The data showed that resting and stress-induced levels of prolactin were decreased by NHCl only. Although neither drug affected the magnitude of the stress-induced ACTH and corticosterone responses, treatment with NHCl, but not NMBr, delayed the poststress decline of these responses. Hence, we concluded that central opiate mechanisms may be important for cessation of HPA axis activity, after exposure to stressful situations.

Adrenocorticotropic Hormone↗
PubMed1990

Effects of chronic stress on in vivo pituitary-adrenocortical responses to corticotropin releasing hormone.

Experimental evidence indicates that animals exposed to chronic stress demonstrate increased adrenocorticotropin (ACTH) and corticosterone (CORT) responses to novel stimuli (facilitation) but attenuated ACTH and CORT responses to the chronic stressor (adaptation). The mechanisms responsible for facilitation and adaptation of ACTH and CORT responses are not known. In the present experiments, we chronically exposed male Fischer-344 rats to sessions of a two-way shock-escape stress procedure following a schedule which we had previously shown to elicit adaptation of ACTH and CORT responses. To determine if pituitary-adrenocortical adaptation to stress was mediated by alterations in pituitary responsiveness to corticotropin-releasing hormone (CRH), control and chronically stressed rats received intra-arterial injections of a low and a high dose of CRH and blood samples from each animal were assayed for ACTH and CORT levels. The results showed that ACTH responses to the low (but not the high) dose of CRH were attenuated by chronic stress. In addition we confirmed previous reports which showed that chronic stress increased adrenocortical sensitivity to ACTH. Thus, we concluded that adaptation of ACTH responses to chronic stress may be in part mediated by a reduction of the CRH-induced ACTH secretory response.

Adrenocorticotropic Hormone↗
PubMed1990

Glucoregulatory responses of adult and aged rats after exposure to chronic stress.

Stress has been implicated as an environmental factor that may accelerate the process of biological aging. However, this proposal has remained largely anecdotal due to relatively few studies that directly tested this hypothesis. In the present experiments groups of 6-month-old and 20-month-old male F-344 rats were chronically stressed for a six-month period. After the last stress session, when the animals were 12 months of age (adult) and 26 months of age (old), control and chronically stressed rats were tested for their ability to: (a) elicit glucose and insulin responses to an acute, novel stressor; (b) remove a circulatory glucose load elicited either by acute stress exposure or by injection of d-glucose; and (c) raise insulin levels after a glucose challenge. In control rats, we observed a deficit in each of these parameters in old compared to adult rats. Exposure to chronic stress did not exacerbate deterioration of these response mechanisms in either adult or old rats. In fact, the data showed a modest improvement in glucose tolerance in chronically stressed compared to age-matched control rats. We conclude that chronic stress did not exacerbate age-dependent decline of glucoregulatory capacity. From these results and from our earlier work, we speculate that the decline during aging of the functional integrity of systems involved in the response to stress may be sustained by periodic challenges from the organism's external environment.

Age Factors↗
PubMed1989

Age-related adaptation of pituitary-adrenocortical responses to stress.

It has been reported that aged rats show impaired feedback regulatory control of pituitary adrenocorticotropic hormone release by adrenal glucocorticoids, yet, show no age-related deficit in eliciting an adrenocortical stress response when compared to younger animals. However, the effects of age on the capacity of the pituitary-adrenocortical system to adapt from an acute to a chronic stress situation have not been fully resolved. In the present study, groups of 6-month-old (young) and 22-month-old (old) F-344 rats were sacrificed at various times during the 1st (day 1) and 3rd (day 3) acute exposure to a two-way electric shock-escape stress procedure and subsequently during the 28th (day 28) and 56th (day 56) chronic exposure. Determinations of stress-induced corticosterone and adrenocorticotropic hormone responses indicated that: (1) adrenocortical responses were similar between young and old rats on the first stress exposure, whereas by the third stress session corticosterone responses were higher in young than in old rats; (2) attenuation of pituitary-adrenal responses to chronic stress was less in old compared to young rats, and (3) environmental factors may delay the development of age-related physiological alterations in the pituitary-adrenocortical system.

Adaptation, Physiological↗
PubMed1989

Age-dependent effects of chronic stress on ACTH and corticosterone responses to an acute novel stress.

Aging effects on the hypothalamic-pituitary-adrenocortical system have been studied primarily in the sedentary, environmentally deprived laboratory rat. Since it is known that chronic activation changes the responsiveness of the hypothalamic-pituitary-adrenocortical system, the present experiments were undertaken to determine whether age-related effects on this system would differ between sedentary and chronically stressed rats. Groups of 6- and 20-month-old F-344 rats were exposed to daily sessions of a 2-way shock-escape procedure over a 6-month period. When the rats were 12 (adult) and 26 months of age (old), pituitary-adrenocortical responses to an acute, novel stimulus were examined in young and old chronically stressed and age-matched control rats. Young and old control rats showed essentially the same corticosterone response to an acute motion stress. Chronic stress exposure increased the corticosterone response to the novel acute stressor in young but not in old rats. ACTH levels in response to acute stress were significantly reduced in old control rats compared to young control animals. Chronic stress did not change the ACTH acute stress response in young animals, whereas in old animals chronic stress elevated the ACTH responsiveness so that the old rats showed stress-induced ACTH levels that were comparable to the young animals. In conclusion, the effects of chronic stress on the function of the hypothalamic-pituitary-adrenocortical system are age-dependent, and environmental factors can significantly influence the progression of aging of the hypothalamic-pituitary-adrenal system.

Acute Disease↗
PubMed1989

Apparent age-related resistance of type II hippocampal corticosteroid receptors to down-regulation during chronic escape training.

Corticosteroids appear to modulate neuronal loss in the hippocampus during aging. However, there is a seeming paradox in the literature in that age-related neuronal loss develops more prominently during the later phases of the lifespan, whereas brain corticosterone receptors have been reported to decline with aging, an effect that might be anticipated to reduce the impact of corticosteroids on cell loss. In order to study the regulatory sensitivity of hippocampal corticosteroid receptors (HCSR) during aging, which could play a role in this apparent paradox, rats of 3 ages (4, 12, and 18 months old at the start of training) were given 6 months of chronic escape training using a mild footshock in a 2-way shuttle-escape task (4 hr/d, 5 d/week). Animals were killed either 1 d or 3 weeks following the 6 month training paradigm. Nontrained home cage controls also were maintained in parallel with each age group. Although previous studies have measured receptors in rats adrenalectomized 12 hr or more prior to death, rats intact at death were used in the present studies to avoid possible confounding effects from age differences in receptor up-regulation or response to surgery. Receptor capacity was analyzed with a saturation assay able to measure available type II HCSR in intact rats. Results showed that, in intact young-mature rats (10 months old at death), type II HCSR were down-regulated at 1 d, but not at 3 weeks, after the end of the 6 months of training. However, significant decreases in HCSR were not observed in late mid-aged (18-month-old) or aged (24-month-old) rats at the 1 d point, indicating apparent resistance to down-regulatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Effects of age on metabolic responses to acute and chronic stress.

The effect of age on the capacity of an organism to mobilize glucose and free fatty acids during stress and to adapt these responses from an acute to a chronic stress situation is not known. The purpose of this study was to determine whether aging impaired the capacity to 1) raise glucose and free fatty acid levels and suppress insulin release in acute stress situations and 2) develop adaptation of these responses to exposure to chronic stress. Our results indicate that 6-mo-old rats (young) trained to escape electric shock (short-term modulation) showed greater acute stress-induced hyperglycemic, hypoinsulinemic, and lipolytic responses than untrained young rats. By contrast, in 22-mo-old rats (old), responses of trained and untrained animals were not different. In the chronic stress (long-term adaptation) experiments, it was found that 1) adaptation of stress-induced hyperglycemia occurred at a faster rate in young than in old animals; 2) in young but not in aged rats, a strong positive correlation was observed between adaptation of stress-induced hyperglycemia and hypoinsulinemia; and 3) in young rats, stress-induced lipolytic responses declined proportionately to the duration of chronic stress exposure, whereas by contrast in chronically stressed aged rats steady-state levels of free fatty acids were not raised during exposure to stress. Thus we conclude that 1) glucose intolerance may play a key role in the altered stress-induced metabolic responses of aged rats; 2) with age, there is a loss of plasticity in physiological adaptive response mechanisms associated with metabolic responses to stress.

Aging↗
PubMed1987

Effects of acute and chronic stress on the neural retina of young, mid-age, and aged Fischer-344 rats.

Male Fischer-344 rats at 5 (young), 11 (mid-age) and 18 (aged) months of age were exposed either to a single, 1-h period of acute stress, or to daily 4-h periods (chronic) of escapable footshock stress for 6 months, and subsequently allowed a one month interval without stress. The influence of age and exposure to stress on the neural retina was examined by histopathologic and morphometric methods. Age changes in the retina of unstressed control animals included reduction in the thickness of the outer nuclear layer (ONL; photoreceptor nuclei) and of the retina, especially in the peripheral areas. The superior hemisphere was more severely affected than the inferior retina. Exposure to acute stress did not influence retinal histopathology. However, in mid-age and aged rats exposed to chronic stress, the ONL and retinal thicknesses were reduced significantly. Our results indicate for the first time that exposure of rats to chronic stress produces changes in retinal morphology that are associated commonly with aging, such as extensive loss of peripheral photoreceptor cells. In addition, the results show that the effects of chronic stress exposure are greatest in aged rats. The effect of light exposure on the aging retina was not investigated since all rats were exposed to the same total photoperiod.

Acute Disease↗
PubMed1987

Effects on immune responses by chronic stress are modulated by aging.

Male Fischer-344 rats at 5, 11, and 18 months of age were exposed to chronic stress for 6 months and subsequently allowed a 1-month interval with no stress before examination of splenic lymphocyte proliferative responses, IL-2 secretion by T cells, and NK cell activity in stressed and age- and sex-matched control animals. All four responses declined as a function of age in control rats. Stress exposure significantly decreased concanavalin A and lipopolysaccharide proliferative responses in 12- and 18-month-old compared to control rats without altering IL-2 secretory capacity. NK cell activity was slightly depressed by stress only in 18-month-old rats. By contrast, in 25-month-old animals that already demonstrated immune response levels lower than those of younger animals, stress did not significantly affect the responses examined. Thus, younger rats were more susceptible to a decline in host-defense responses induced by long-term chronic stress than older rats. Overall, the data suggest that aging significantly and differentially modulates the ability of environmental stress to influence the immunocompetent status of the organism.

Aging↗
PubMed1987

Diminished diurnal secretion of adrenocorticotropin (ACTH), but not corticosterone, in old male rats: possible relation to increased adrenal sensitivity to ACTH in vivo.

The diurnal secretion of ACTH and corticosterone was examined in chronically cannulated young (3-4 months old), middle-aged (10-12 months old), and old (22-24 months old) Fischer 344 male rats. Plasma corticosterone in young rats increased from baseline concentrations of 78 +/- 5 to a maximum of 171 +/- 24 ng/ml at 1730 h and declined to basal levels by 1930 h. Middle-aged and old rats demonstrated a similar magnitude and time course of corticosterone release. However, comparison of the relative concentrations of ACTH released during the diurnal surge revealed that old rats secreted 35% less ACTH than young or middle-aged animals (P less than 0.05). Age-related changes in the sensitivity of the adrenal gland to a submaximal dose of ACTH were tested in dexamethasone-pretreated animals at 1100 and 1700 h in a separate experiment. Plasma corticosterone levels were significantly greater after ACTH administration (1 mIU/kg ACTHAR, iv) at 1700 h in both young and old rats compared to 1100 h values (P less than 0.05), and levels 20 min post-ACTH injection at 1700 h were significantly greater in old than young or middle-aged rats at the same time (P less than 0.05). These results demonstrate that 1) there are no age-related changes in the diurnal secretion of corticosterone in Fischer 344 male rats; 2) there is a decline in the peak level of ACTH during the diurnal surge of old compared to young animals; and 3) adrenal sensitivity to ACTH at 1700 h is greater in old compared to young or middle-aged rats. We hypothesize that the greater increase in adrenal sensitivity to ACTH is responsible for the maintenance of the corticosterone rhythm in the presence of diminished ACTH concentrations in older rats.

Adrenocorticotropic Hormone↗
PubMed1986

Impairment of immune function after cessation of long-term chronic stress.

A pronounced impairment of mitogen-induced proliferation of splenic lymphocytes was observed in Fischer-344 male rats 1 month after termination of exposure of the animals to stress. The stress model used in these experiments was random schedules of a signaled, escapable electric foot-shock stress for 2-4 h/day over a period of 6 months. The magnitude of the observed immunosuppression correlated positively with the total, cumulative stress exposure received by the animals. The effect was not secondary to changes in the percentage of splenic T lymphocytes in stressed, compared to control rats. Also, at the time of sacrifice, plasma levels of corticosterone were comparable in experimental and control animals. Therefore, the immunosuppression observed 1 month after the last stress session cannot be attributed to pituitary-adrenocortical hyperactivity, at the time of sacrifice. These results provide the first evidence that stress-induced immunosuppression is not restricted to the period of exposure to the stress. This finding may contribute to a better understanding of the suggested association between stressful life events and increased susceptibility to disease in humans.

Animals↗
PubMed1985

Neuronal damage in the rat retina after chronic stress.

Long-term exposure to escapable foot shock has been used to determine if chronic stress influences neuronal cell death in the retina of albino and pigmented rats. Histopathologic and morphometric approaches analyzed changes in photoreceptors and neurons of the bipolar and ganglion cell layers of the retina. Albino Fischer rats when exposed to chronic stress for 4-8 h daily for 1 week to 6 months, developed severe retinal damage, as compared to unstressed control retinas, with reduction in photoreceptor and bipolar neurons, particularly in the superior central retina. The damage was observed in male and female rats, but males appeared to be more susceptible to the influence of stress than female animals. Ganglion cells were unaffected. Photoreceptor destruction did not occur in Long-Evans pigmented rats under identical experimental conditions. The results suggest that: input of the sensory stimulus, light, to the retina of stressed rats augmented neuronal damage and might be required for its initiation; and hormones and/or neurotransmitters associated with long-term chronic stress might be related to increased neuronal cell death in the mammalian retina.

Albinism↗
PubMed1980

ACTH regulation of tissue-CRF.

The influence of the anterior pituitary on tissue CRF was investigated in two sets of experiments using lesioned, hypophysectomized, adrenalectomized donor rats. Donors were injected with 1 or 0.5 anterior pituitary equivalents 3 h before transfer of plasma to recipient animals. Injection of 1 pituitary equivalent significantly reduced levels of corticosterone in recipient rats compared to saline injection at 3 different time intervals following the transfer. In a second series of experiments donor animals received replacement with saline, ACTH, TSH, or PRL at 0, 2 and 4 h following adrenalectomy; transfer of plasma to recipient animals was at 5 h. Of the three hormones injected only ACTH significantly reduced tissue CRF activity in donor animals. Recipients of these donors showed suppressed levels of corticosterone compared to recipient animals whose donors were injected with saline, TSH or PRL. The ACTH dose-response curve indicates that the effective dose for suppression of tissue CRF in donor animals is in the range of 1-10 mU/ml. Results of these experiments clearly show that tissue CRF is inhibited by the anterior pituitary hormone ACTH rather than by elevated levels of corticosterone. These experiments suggest that feedback regulation of tissue CRF release by ACTH may occur in response to prolonged physical stress.

Adrenalectomy↗