Insulin acts on the hypothalamic glucose-facilitated neurons to induce hyperglycemia and hyperinsulinemia in the rat

Microinjection of insulin (0.04–0.12 IU/l) into the anterior hypothalamus or the lateral hypothalamus, but not the vertromedial hypothalamus of the rat brain, caused a dose-dependent rise in blood glucose and in serum insulin. The majority (71.5%) of the glucose-facilitated neurons recorded in the lateral hypothalamic area were excited by intracerebral injection of insulin. The data indicate that insulni acts on the hypothalamic glucose-facilitated neurons to induce hyperglycemia and hyperinsulinemia. It is unknown whether insulin normally reaches the hypothalamic area, or how it might do so.This work was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China).     

Insulin can induce the expression of a memory-related synaptic protein through facilitating AMPA receptor endocytosis in rat cortical neurons

Learning and memory depend on long-term synaptic plasticity including long-term potentiation (LTP) and depression (LTD). Activity-regulated cytoskeleton-associated protein (Arc) plays versatile roles in synaptic plasticity mainly through inducing F-actin formation, underlying consolidation of LTP, and promoting AMPA receptor (AMPAR) endocytosis, underlying LTD. Insulin can also induce LTD by facilitating the internalization of AMPARs. In neuroblastoma cells, insulin induced a dramatic increase in Arc mRNA and Arc protein levels, which may underlie the memory-enhancing action of insulin. Thus, a hypothesis was made that, in response to insulin, increased AMPAR endocytosis leads to enhanced Arc expression, and vice versa. Primary cultures of neonatal Sprague–Dawley rat cortical neurons were used. Using Western-blot analysis and immunofluorescent staining, our results reveal that inhibiting AMPAR-mediated responses with AMPAR antagonists significantly enhanced whereas blocking AMPAR endocytosis with various reagents significantly prevented insulin (200 nM, 2 h)-induced Arc expression. Furthermore, via surface biotinylation assay, we demonstrate that acute blockade of new Arc synthesis after insulin stimulation using Arc antisense oligodeoxynucleotide prevented insulin-stimulated AMPAR endocytosis. These findings suggest for the first time that an interaction exists between insulin-stimulated AMPAR endocytosis and insulin-induced Arc expression.     

Electrophysiology of mammalian hypothalamic and interpeduncular neurons in vitro

Summary Electrical activities of the hypothalamic and interpeduncular neurons were studied in vitro in brain slices prepared from the guinea-pig brain stem. Neurons preserved resting membrane potentials comparable to those of neurons in vivo, responded to stimulation of the afferent fibres, and retained stable spontaneous firings for more than several hours.     

Increase in the hypothalamic tyrosine hydroxylase activity after lesion of the catecholaminergic neurons of the rat pontine tegmentum]

Hypothalamic tyrosine hydroxylase activity is increased 6 and 18 h after bilateral lesioning of the Locus Coerulues, in the Rat. An adrenocortical hypertrophy was observed previously, under the same experimental conditions. The neurochemical and neuroendocrinological implications of theses results are discussed.     

Electrophysiology of mammalian hypothalamic and interpeduncular neurons in vitro.

Electrical activities of the hypothalamic and interpeduncular neurons were studied in vitro in brain slices prepared from the guinea-pig brain stem. Neurons preserved resting membrane potentials comparable to those of neurons in vivo, responded to stimulation of the afferent fibres, and retained stable spontaneous firings for more than several hours.     

Failure of3H-serine to induce radioactivity in presumed glycinergic retinal neurons

Summary ³H-serine does not label retinal neurons selectively when injected intraocularly in rabbits, as would have been expected if it had been converted to neutrotransmitter glycine. The reason is unknown, but one possibility is that the conversion was blocked during the conditions of the experiment.This work was supported by the Swedish Medical Research Council (project No. 04X-2321) and the Faculty of Medicine, University of Lund.     

Glutamate decarboxylase activity in preoptic and hypothalamic nuclei of the rat

Summary Freeze-dried samples were used for the determination of glutamate decarboxylase activity in discrete preoptic and hypothalamic nuclei. The activity showed marked regional variation in distribution.     

Fluorescence histochemical demonstration of the uptake of dopamine-derived dihydroisoquinoline in the hypothalamic neurons

Summary The uptake and the accumulation of dopamine-derived fluorescent dihydroisoquinoline were demonstrated with direct fluorescence histochemistry in the hypothalamic dopaminergic neurons, in the nerves of the neurointermediate lobe, and in some endocrine cells of the hypophysis of the rat.     

Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat

Summary Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that bothV _max andK _m were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH₄ cofactor. TP replacement to castrate rats increased theK _m for added DMPH₄ cofactor, whileV _max decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzymereduced pteridine cofactor complex.     

The hypothalamic somatostatinergic pathways mediate feeding behavior in the rat

The level of somatostatin in the hypothalamus was higher in satiated rats than in hungry rats. Elevating hypothalamic somatostatin levels by administering somatostatin into the hypothalamus produced a decrease in food intake, whereas lowering hypothalamic somatostatin levels by administering cysteamine into the peritoneal cavity produced an increase in food intake in rats.     

Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat.

Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex.     

The effect of continuously cooling the hypothalamic preoptic area on antibody titre in the rat

Summary Continuous cooling of the hypothalamic preoptic area for 5 days, as well as sublethal infection withSalmonella enteritidis, increased the titre of antibodies against sheep erythrocytes, suggesting that the febrile response stimulates the humoral immune response.We thank Dr W. Mannheim from the Institute of Hygiene for kindly supplying the cultures ofS. enteritidis. This work was supported by the Schwerpunktprogramm Temperaturregulation und-adaptation of the Deutsche Forschungsgemeinschaft.     

Interaction between the effects of centrally administered arecoline and leucocyte pyrogen on the activity of posterior hypothalamic neurons in the rabbit

In experiments with urethane-anesthetized rabbits, the alteration in the activity of posterior hypothalamic neurons resulting from intracerebroventricular injection of leucocyte pyrogen was attenuated by subsequent administration of arecoline. Atropine failed to alter the neuronal response to leucocyte pyrogen but abolished the effect of arecoline. The neuronal response to arecoline was reversed in the absence of leucocyte pyrogen.     

Interaction between the effects of centrally administered arecoline and leucocyte pyrogen on the activity of posterior hypothalamic neurons in the rabbit

Summary In experiments with urethane-anesthetized rabbits, the alteration in the activity of posterior hypothalamic neurons resulting from intracerebroventricular injection of leucocyte pyrogen was attentuated by subsequent administration of arecoline. Atropine failed to alter the neuronal response to leucocyte pyrogen but abolished the effect of arecoline. The neuronal response to arecoline was reversed in the absence of leucocyte pyrogen.     

Cilia in stellate neurons of the rat cerebellum

Summary Cilia in stellate neurons of the normal rat cerebellum are described. 8 cilia were observed in a total of 60 cells studied. An 8+1 pattern was found throughout their length. Furthermore, no arms, spokes or other accessory structures necessary for ciliary motion were seen. These findings make it possible to suggest that these cilia are probably without function and are related to the epithelial origin of these cells.This work was granted by INIC: Centro de Morfologia Experimental (MbP₁).Acknowledgments. The authors thank M.A. Rodrigues, M. M. Pacheco, M. C.Pinho and L. B. Nunes for technical assistance.