Biomedical subjects

E M Stricker

Publications and source records attributed to E M Stricker.

At least 109 records · Page 6Linked to original sources

PubMed1985

Effect of chronic cold exposure on tyrosine hydroxylase mRNA in rat adrenal gland.

The effect of chronic stress on the levels of tyrosine hydroxylase (TH) RNA in rat adrenal gland was investigated by RNA-DNA hybridization using a cloned TH cDNA probe. Results of dot-blot hybridization experiments and northern analysis demonstrate that exposure of animals to cold for 1 week results in a 4-5-fold increase in the relative abundance of TH mRNA. This increase in TH mRNA level may underlie the increase in adrenal TH activity that is known to occur when rats are exposed to such cold stress.

Adrenal Medulla↗

PubMed1985

Hyperinnervation of the striatum by dorsal raphe afferents after dopamine-depleting brain lesions in neonatal rats.

Dopamine-depleting brain lesions produced in neonatal rats by intraventricular injection of 6-hydroxydopamine (6-OHDA) are known to increase striatal levels of serotonin by adulthood. We now report that such lesions lead to an increased innervation of the striatum by serotonin-containing neurons from the dorsal raphe nucleus. This hyperinnervation was revealed as a 300% increase in the number of retrogradely labeled neurons in the dorsal raphe after horseradish peroxidase was injected into the adult striatum. The degree of hyperinnervation was reduced sharply when serotonin-depleting brain lesions were given to adult animals that had received 6-OHDA as neonates.

5,7-Dihydroxytryptamine↗

PubMed1985

Stress-induced neurological impairments in an animal model of parkinsonism.

Adult rats were given the neurotoxin 6-hydroxydopamine (6-HDA) by means of cerebrospinal fluid to produce large dopamine-depleting brain lesions. Although the animals behaved normally in their home cages, they became akinetic after such treatments as glucoprivation, tail shock, and exposure to severe cold. The neurological impairments were related both to the extent of dopamine depletion and to the intensity of the stress. Drugs known to enhance dopaminergic function were found to reverse the stress-induced neurological deficits, while dopaminergic antagonists potentiated the debilitating effects of stress. After focal lesions were produced by injecting 6-hydroxydopamine directly into specific brain regions, stress-induced akinesia was found to correlate best with dopamine depletion in the corpus striatum, especially the lateral portion of that structure. These and other findings suggest that the acute emergence of parkinsonian symptoms during stress may reflect extensive damage to the dopaminergic nigrostriatal pathway that had been concealed in a preclinical phase, owing to compensatory neurochemical changes in the dopaminergic neurons that yet remain intact.

Animals↗

PubMed1985

Visceral factors in the control of food intake.

Some years ago, we reported that the increased blood intake of hypoglycemic rats was inhibited by the intravenous infusion of fructose, a sugar that cannot cross the blood-brain barrier and nourish cerebral chemoreceptors. More recent experiments therefore have focused on visceral factors in the control of food intake. Three observations have been emphasized in this review. First, we found that gastric emptying was increased during insulin-induced hypoglycemia, and that this effect also was eliminated by administration of fructose. Hepatic vagotomy abolished both this effect of fructose on gastric emptying and its effect on food intake. Second, we found that in rats with severe diabetes, the rate of gastric emptying did decrease in proportion to increasing concentration of an administered glucose load, as it does in intact rats, but calories emptied more rapidly than normal regardless of the concentration of the load. Third, we found that rats with varying degrees of streptozotocin-induced damage to the pancreas ate more food than intact rats did after an overnight fast, and that individual intakes were proportional to the induced glucose intolerance. The increased eating took the form of shorter intermeal intervals, as if the initial postfast meal did not remain satiating for a normal amount of time. These and other findings suggest that food intake is controlled in part by satiety signals apparently related to the delivery of utilizable calories plus insulin to the liver. These signals also seem to affect gastric emptying and thereby might influence other satiety signals related to gastric distention.

Animals↗

PubMed1985

Effects of lateral hypothalamic lesions on food intake of rats during exposure to cold.

Lateral hypothalamic damage impaired both physiological and behavioral responses of rats during exposure to a 5 degree C environment. The brain-damaged animals usually did not conserve heat in the cold as well as control rats did, nor did they always increase their caloric intake to meet their energy needs. However, when given sucrose solution to drink instead of water, they did increase their ingestion of chow in response to cold exposure. It is likely that the elevated consumption of palatable fluid served to relieve dehydration and thereby removed its constraints on eating, thus permitting hyperphagia to occur. In contrast to these results, rats with large dopamine-depleting brain lesions, produced by intraventricular 6-hydroxydopamine treatments, always increased food intake when exposed to cold stress and demonstrated no apparent problems in peripheral vasoconstriction. Thus, it is unlikely that striatal dopamine depletions account for either the impaired feeding response or the inadequate heat conservation of rats with lateral hypothalamic lesions during cold stress.

Animals↗

PubMed1985

Rats given dopamine-depleting brain lesions as neonates are subsensitive to dopaminergic antagonists as adults.

Extensive damage to central dopamine (DA)-containing neurons are known to produce akinesia and sensory neglect when the lesions are made in adult rats. Similar behavioral impairments occur when dopaminergic function is disrupted temporarily by DA receptor blocking agents, and brain-damaged rats are particularly sensitive to the effects of those drugs. The present experiments offer a striking contrast to these well-accepted findings that central DA-containing neurons are critical to the initiation of voluntary movement. After near-total destruction of the dopaminergic neurons in 3-day-old rats, there were no conspicuous behavioral dysfunctions at any time during the subsequent 5-8 months, even when the animals were given large doses of DA receptor blocking agents. These findings suggest that some other neuronal system had replaced the absent dopaminergic neurons in the central control of movement.

Age Factors↗

PubMed1985

Hyperdipsia in rats after electrolytic lesions of nucleus medianus.

Ablation of the ventral portion of nucleus medianus (vNM) in rats produced a temporary adipsia or hypodipsia that was accompanied by pronounced urinary fluid losses. When ad libitum drinking resumed, about half of the brain-damaged animals became hyperdipsic, exhibiting chronic two- to threefold elevations in their daily water intakes during the nocturnal hours of the day-night cycle. Rats that remained normodipsic after vNM ablation usually exhibited hyperdipsia if they were food-deprived overnight. The basis for the hyperdipsia produced by vNM ablation was not clear. The elevated water intakes appeared not to result from chronic urinary fluid losses, because hyperdipsic rats were able to concentrate their urine during the day, when they drank little. Moreover, the animals did not seem to be volume depleted; their plasma renin activities were not elevated, and they drank normally in association with meals. These and other findings suggest that vNM lesions damage neural substrates that control drinking behavior, and the hyperdipsia results from this rather than from physiological changes produced by the lesion.

Animals↗

PubMed1985

Impaired drinking responses of rats with lesions of nucleus medianus: circadian dependence.

The drinking behavior of rats with electrolytic lesions of ventral nucleus medianus (vNM) was examined during acute hyperosmolality and hypovolemia. The brain-damaged animals were impaired in their drinking responses to systemic treatment with hypertonic saline or polyethylene glycol solution when they were tested during the day. However, apparently normal drinking responses to both dipsogenic challenges were observed when the same animals were pretreated with the stimulant drug, caffeine, or when they were tested at night. These results suggest that lesions of vNM may produce complex alterations in the control of drinking behavior rather than the destruction of sensory receptors. The lesions appear to disrupt both circadian influences on drinking and activational components of drinking that normally serve to facilitate the behavioral response. The present results, together with similar findings for rats given lesions of the subfornical organ, support recent proposals that periventricular tissue bordering the rostral wall of the third cerebral ventricle plays an important role in the central control of drinking.

Animals↗

PubMed1985

Impaired secretion of vasopressin and oxytocin in rats after lesions of nucleus medianus.

Regulation of posterior pituitary secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats given electrolytic lesions of ventral nucleus medianus (vNM). As described previously, rats with such lesions were chronically hypernatremic and showed impaired drinking responses to an osmotic challenge. AVP secretion in response to osmotic stimuli also was significantly blunted, although sufficient increases in plasma AVP levels did occur, in association with an abnormally high range of plasma sodium concentrations, to allow urinary concentration comparable to control animals. These findings suggest that vNM lesions cause an upward resetting of the osmotic threshold for AVP secretion. In contrast, hypovolemia, produced by subcutaneous polyethylene glycol treatment, and hypotension, produced by phentolamine treatment, both evoked AVP responses in rats with vNM lesions that were equivalent to those seen in control animals. Plasma OT responses to osmotic and hemodynamic stimuli were analogous to the AVP responses. These findings reproduce the major clinical features observed in humans with the disorder of essential hypernatremia and by doing so support proposals that this disorder is caused by lesions in the vicinity of the anterior hypothalamus that result in selective destruction of afferent osmosensitive inputs to the neurohypophysis.

Animals↗

PubMed1985

Neural control of adenylate cyclase responsiveness in brown adipose tissue.

The level of prior adrenergic stimulation is known to affect the responsiveness of tissue to subsequent stimulation. We investigated the effects of cold exposure on sympathetic nerve activity in interscapular brown adipose tissue (IBAT) and the impact of those changes on the responsiveness of the adenylate cyclase system. Exposing rats to 4 degrees C for 3 days increased norepinephrine turnover in IBAT and increased the ability of norepinephrine to stimulate adenylate cyclase activity. This 2- to 3-fold increase in adenylate cyclase activity appeared to result from increased nerve transmission because it was abolished by prior surgical denervation of IBAT. Additional studies indicated that cold exposure did not affect the number of beta adrenergic receptors in IBAT. Moreover, cold exposure increased the maximal response of adenylate cyclase to fluoride and guanosine-5--(beta-gamma-imino)triphosphate stimulation by 2- to 3-fold. We conclude that increased nerve transmission produces supersensitivity of IBAT adenylate cyclase and this effect is mediated by a postreceptor modification of the adenylate cyclase system.

Adenylyl Cyclases↗

PubMed1985

Tyrosine hydroxylase activity and catecholamine biosynthesis in the adrenal medulla of rats during stress.

Chronic hypotension and hypoglycemia are known to increase the capacity for catecholamine biosynthesis in the rat adrenal medulla by increasing the maximal velocity of the rate-limiting enzyme, tyrosine hydroxylase (TH). The present report indicates that the gradual increase in maximal TH activity is preceded by a more rapid increase in the affinity of TH for its pterin cofactor. These short-term alterations in adrenal TH activity are related to the severity of the stress, associated with parallel changes in catecholamine biosynthesis, and prevented by prior adrenal denervation. In contrast, cold exposure, which leads to comparable long-term increases in adrenal TH activity, does so without causing a prior activation of TH. However, adrenal TH is activated by acute cold exposure if the sympathetic nerves, that normally are stimulated during cold, are destroyed previously by 6-hydroxydopamine treatment. These and other observations suggest that alterations in adrenal TH activity vary according to the type and duration of physiological stress, and may be mediated by temporally distinct processes.

Adrenal Medulla↗

PubMed1985

Tyrosine hydroxylase activity in the sympathoadrenal system under basal and stressful conditions: effect of 6-hydroxydopamine.

Subtotal destruction of central noradrenergic neurons with the neurotoxin, 6-hydroxydopamine, is known to increase tyrosine hydroxylase (TH) activity within surviving nerve terminals. The present report demonstrates a similar, dose-related elevation of TH activity in the adrenal medulla and sympathetic nerves after systemic 6-hydroxydopamine treatment. Two temporally distinct processes were observed in the sympathetic nerves: a rapid activation of TH, present during the first few days after the lesion, and a more gradual increase in maximal TH activity, most probably due to enzyme induction. In this regard, the stimulatory effect on catecholamine biosynthesis of cyclic AMP-dependent phosphorylation was attenuated substantially within cardiac sympathetic nerves 3 days after the lesion, but by 3 weeks the efficacy of cyclic AMP-dependent phosphorylation was restored completely. Similarly, the normal activation of cardiac TH activity elicited by insulin-induced hypoglycemia and cold stress was absent soon after 6-hydroxydopamine treatment, but returned 3 weeks later. These latter findings suggest that the adaptations within the sympathoadrenal system after subtotal sympathectomy can preclude further adaptations to stress.

Adrenal Medulla↗

PubMed1984

Partial damage to the noradrenergic bundle increases tyrosine hydroxylase activity in noradrenergic terminals of hippocampus but not cerebellum.

Intracerebral administration of 6-hydroxydopamine (6-HDA) along the dorsal noradrenergic bundle produced a gradual and long-lasting decrease of norepinephrine (NE) in hippocampus. This decrease in NE levels initially was accompanied by a parallel decrease in the activity of the rate-limiting enzyme for NE biosynthesis, tyrosine hydroxylase (TH). However, by 14 days the decrease in enzyme activity was much less pronounced than that of NE levels, resulting in an 8-fold increase in the ratio of TH activity to NE content. This persisted for at least two months, the longest time examined. Depletion of NE and changes in TH activity were not observed in cerebellum after the 6-HDA treatment. The selective increase in the ratio of TH activity within denervated regions may reflect an adaptation to the lesion whereby residual noradrenergic neurons increase their synthesis and release of NE.

Animals↗

PubMed1984

Parkinson's disease: studies with an animal model.

Parkinson' disease has been associated with degeneration of dopamine-containing neurons of the nigrostriatal bundle. Many neurological features of Parkinsonism can be produced in rats by selective destruction of central dopaminergic neurons using the neurotoxin 6-hydroxydopamine. In this review we discuss two aspects of Parkinson's disease that have been investigated in these animals. First, we consider why near-total degeneration of nigrostriatal bundle neurons is required before neurological symptoms emerge. It appears that the loss of dopaminergic neurons is accompanied by an exponential increase in the ratio of tyrosine hydroxylase activity to dopamine content. Thus, after the brain lesions there may be a compensatory increase in the capacity of residual dopaminergic neurons to synthesize and release transmitter. Second, we consider why stress produces severe neurological deficits in patients who are only mildly impaired otherwise. It appears that a variety of stressors produce an abrupt but transient increase in dopaminergic activity in the striatum of intact animals and that this increase is markedly attenuated by 6-hydroxydopamine treatment. Thus, stress-induced akinesia in animals with dopamine-depleting brain lesions and in Parkinsonian patients may result from the impaired ability of residual neurons to respond approximately to such stimuli.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats.

Near-total dopamine-depleting brain lesions produced in 3-day-old rats by intracerebroventricular injection of the neurotoxin 6-hydroxydopamine led to pronounced increases in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid contents 1-8 months later. This effect was associated with an increase in in vitro high affinity 5-HT uptake, suggesting that proliferation of new serotonergic terminals had occurred within the striatum. No such effect was obtained when comparable brain lesions were produced in adult rats.

Animals↗

PubMed1984

Neurochemical compensation after nigrostriatal bundle injury in an animal model of preclinical parkinsonism.

Parkinson's disease usually involves a lengthy preclinical period during which few neurological symptoms are observed despite extensive damage to the dopaminergic nigrostriatal bundle. Injury to this projection in the rat also fails to produce major neurological dysfunctions. In our studies, damage to the nigrostriatal bundle of the rat, resulting in the loss of up to 95% of the dopaminergic terminals in striatum, was accompanied by apparent increases in the synthesis and release of dopamine (DA) from those dopaminergic terminals that remained. More specifically, both the activity of the rate-limiting biosynthetic enzyme, tyrosine hydroxylase, and the content of the principal DA metabolite, dihydroxyphenylacetic acid, were increased in striatum relative to DA levels. The increases were exponentially related to DA loss.

Animals↗

PubMed1984

Increased feeding by rats after subdiabetogenic streptozotocin treatment: a role for insulin in satiety.

Rats given streptozotocin showed varying degrees of glucose intolerance, ranging from mild to overt symptoms of diabetes mellitus. After being deprived of food overnight, both mild and overt diabetics consumed more food than controls did during 5-hr or 7-hr feeding tests. All animals ate large amounts of food during the first hour of the tests, but both groups of diabetics began to eat again sooner than controls did. Rats demonstrating the greatest degree of glucose intolerance before the test ate the most during the test. These and other findings suggest that feeding by diabetic rats after an overnight fast is an inverse function of their residual capacity for glucose utilization, which occurs despite elevations in blood glucose levels, and is not simply a compensatory response to glucose loss in urine. A modified glucostatic hypothesis is proposed in which insulin may normally promote satiety by influencing peripheral metabolism and making ingested calories utilizable.

Animals↗

PubMed1984

Effect of dopamine-depleting brain lesions on suckling and weaning in rats.

Rats given large dopamine-depleting brain lesions as adults exhibit severe impairments in ingestive behavior and sensorimotor function. In contrast to these well-known effects, virtually complete destruction of central dopaminergic neurons produced no such dysfunctions when it occurred in neonates. Indeed, rats continued to suckle and grow, albeit somewhat more slowly, and they could be weaned readily when they were 27 days old. Although most brain-damaged animals did not survive weaning when they were 18 days old, whereas controls exhibited no difficulty, this failure appears to be the consequence of their reduced body weight and related inability to maintain body temperature in a relatively cool environment (22 degrees C). Such premature weaning occurred more successfully when growth was stimulated by rearing brain-damaged pups in small litters or when ambient temperatures were raised to 31 degrees C so as to minimize heat loss. These results demonstrate that the effects of near-total dopamine-depleting brain lesions are considerably less severe when they occur in infants than when they occur in adults, and, consequently, they reveal a capacity for neural plasticity during development that is no longer present at maturity.

Animals↗