Massako Kadekaro

Local Cerebral Glucose Utilization Is Increased in Acutely Adrenalectomized Rats

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute adrenalectomy on local cerebral glucose utilization in conscious albino rats. Five hours following removal of the adrenal glands, glucose utilization was increased (4-55%) throughout the brain, particularly in the locus ceruleus, hypothalamic paraventricular nucleus, hippocampus, median eminence and anterior lobe of the pituitary gland. These structures are involved in the regulation of corticotropin-releasing factor, vasopressin, and adrenocorticotropic hormone. Treatment with dexamethasone (0.25 mg/kg i.m.) substantially reduced or prevented the stimulatory effects of adrenalectomy on cerebral glucose metabolism. These results demonstrate: (1) the existence of a negative feedback loop between the brain and adrenal glands in which corticosteroids exert an inhibitory action on glucose utilization of brain regions participating in adrenotropic regulation, and (2) a general inhibitory action of glucocorticoids on cerebral metabolism.

Neural systems responsible for the gastric secretion provoked by 2‐deoxy‐D‐glucose cytoglucopoenia.

1. The central structures responsible for the gastrosecretory effect of cytoglucopoenia caused by 2‐deoxy‐D‐glucose (2‐DG) were investigated in 105 cats prepared with chronic gastric fistulae and subjected to various experimental procedures. 2. Bilateral electrolytic lesion of the caudalmost two thirds of globus pallidus almost suppressed the secretory response and caused aphagia and adipsia. 3. Secretion in response to 2‐DG and feeding behaviour were entirely blocked after making a lesion in a large ventromedial area of the meso diencephalic transition comprising the ventral tegmental area of Tsai, the ventral tegmental decussation, the red nucleus, a ventral portion of the central grey matter, the interstitial nuclei of Darkschewitsch and of Cajal, the pre‐rubral fields, the reticular part of substantia nigra, the internal portion of the cerebral peduncle and the ventral part of the mesencephalic reticular formation. 4. Microinjection of 2‐DG in the medial forebrain bundle, at the level of the hypothalamus, caused intense gastric secretion, whereas the same procedure was totally ineffective when the caudalmost two thirds of the globus pallidus were stimulated. 5. Increasing doses of 2‐DG, systemically injected, restored the secretory response in volume and acid concentration and output after intercollicular transection of the brain stem. After the transection, secretion of pepsin was only slightly increased when large doses of 2‐DG were administered, thus suggesting a differential control of water, acid and pepsin secretion in response to cytoglucopoenia. 6. It is concluded that there are at least three reflex systems involved in gastric secretion due to cytoglucopoenia: (a) a reflex consisting of afferent and efferent pathways in the medial forebrain bundle area; (b) a reflex whose afferent side is from the hypothalamus and efferent side is from the globus pallidus; (c) a reflex with the afferent side probably originating in the liver and the efferent side in the lower brain stem. 7. The pathways involved in the first two arcs run along Nautas limbic mid‐brain circuit. The three systems are possibly related to control of secretion and feeding behaviour.

Effects of acute administration of caffeine on local cerebral glucose utilization in the rat

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

The central noradrenergic system in the rat: Metabolic mapping with α-adrenergic blocking agents

Summary Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy- d -[14C]glucose technique in 73 normal, awake rats treated with different doses of the α-adrenergic blockers, phenoxybenzamine, phentolamine and yohimbine. Three types of responses were elicited by the administration of these drugs. The predominant effect observed after administration of all α-blockers was a widespread depression of glucose utilization, particularly within the neocortex. The effect was most pronounced with phenoxybenzamine. In a few structures (locus coeruleus, interstitial nucleus of the stria terminalis, medial forebrain bundle, periventricular nucleus and some medullary and hypothalamic nuclei associated with the regulation of blood pressure24) marked increases in glucose utilization were observed. Administration of phentolamine resulted in increased glucose utilization in all the central components of the auditory system (cochlear n., superior olivary n., n. lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). Phenoxybenzamine and yohimbine tended to decrease glucose utilization in the auditory system. Alternating columns with higher and lower rates of local glucose consumption were observed in most of the neocortical areas and in the cerebellar vermis. The significance of these columns is not clear.

Alterations of local cerebral glucose utilization during chronic dehydration in rats.

The quantitative autoradiographic deoxyglucose method was used to study changes in local cerebral glucose utilization in conscious dehydrated rats. Animals were either given saline to drink or were deprived of water for 5 days. Saline ingestion did not alter the rates of glucose metabolism in any brain region when compared to the rates of glucose metabolism in animals which had free access to water. Glucose utilization was increased by 140%, however, in the pituitary neural lobe. Water deprivation produced both increases and decreases in glucose metabolism, depending on the particular structure. In 20 of 44 brain structures analyzed, there were significant decreases from -18 to -34% in glucose utilization. Four forebrain structures, the subfornical organ, septal triangular nucleus, and hypothalamic paraventricular and supraoptic nuclei, had increases in glucose utilization of 30-73%. The rate of glucose utilization in the pituitary neural lobe was increased by 367% in water-deprived rats. The results demonstrate that metabolic activity is stimulated in some, but not all, of the structures participating in fluid regulation during an intense thirst challenge. Many brain regions have depressed metabolism in chronic severe dehydration.

Selective metabolic stimulation of the subfornical organ and pituitary neural lobe by peripheral angiotensin II

The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, we examined the effects of intravenous infusion of angiotensin II on the rate of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar1-leu8-angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornical organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, was administered to homozygous Brattleboro rats, which normally have elevated rates of glucose utilization in the subfornical organ. Captopril reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II stimulates glucose metabolism in the subfornical organ under conditions in which it provokes drinking and pressor responses. The findings suggest that circulating angiotensin II is responsible for the high rate of glucose utilization observed in the subfornical organ of Brattleboro rats homozygous for diabetes insipidus.

Elevated glucose utilization in subfornical organ and pituitary neural lobe of the Brattleboro rat

Homozygous Brattleboro rats have a genetic inability to synthesize vasopressin and therefore manifest the signs and symptoms of diabetes insipidus. Measurement of local cerebral glucose utilization in these rats has revealed increases specifically localized to the subfornical organ and pituitary neural lobe. Vasopressin replacement reverses the increased glucose utilization only in the subfornical organ. The results suggest that vasopressin regulates the rate of glucose metabolism in the subfornical organ.

Site of action of 2‐deoxy‐D‐glucose mediating gastric secretion in the cat

1. Site of action of 2‐deoxy‐ D‐glucose (2‐DG) responsible for its effect on gastric secretion was investigated in cats prepared with polyethylene or nylon cannulae chronically implanted in the antrum.

Metabolic mapping in the sympathetic ganglia and brain of the spontaneously hypertensive rat

Local rates of glucose utilization in the superior cervical, cardiac, and coeliac ganglia were measured by means of the autoradiographic 2-deoxy-d-[14C]glucose method in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), 32–34, 46–48, and 78–87 days old. Brain glucose utilization was examined in 78–87-day-old SHR and WKY. At 32–34 days (at which time mean arterial blood pressure was normal and similar in both groups of rats), the rates of glucose utilization of all three sympathetic ganglia were the same in both groups. At 46–48 days, despite the fact that blood pressure had risen significantly in SHR (mean ± SEM, 136 ± 3 mm Hg, n = 5, compared to 113 ± 3 mm Hg, n = 5, in the control WKY), glucose utilization was decreased in the cardiac and coeliac ganglia but not in the superior cervical ganglia of the SHR. At 78–87 days, glucose utilization was reduced in all the sympathetic ganglia of the hypertensive rats. These results suggest that the sympathetic system is less active in SHR and indicate that hyperactivity of the sympathetic nervous system is not part of the mechanism of the hypertension. Of 44 structures examined in the central nervous system, only the external cuneate, vestibular, and fastigial nuclei of the SHR exhibited increased rates of glucose utilization, and no changes were found in any of the other structures. These increases are probably not related to the origin or maintenance of the hypertension, inasmuch as lesioning of the vestibular or fastigial nuclei did not decrease blood pressure in the SHR.

Metabolic mapping of neural pathways involved in gastrosecretory response to insulin hypoglycaemia in the rat

1. The central nervous structures involved in the gastrosecretory effect of insulin hypoglycaemia were investigated in twenty urethane‐anaesthetized rats, previously provided with a chronic gastric fistula, by means of the 2‐deoxy‐ D‐[14C]glucose autoradiographic technique.