An acute hyperglycemia or acidosis-induced changes of indolamines level correlates with PKC-alpha expression in rat brain.

Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal's results in altered brain neurotransmitter levels. In this study, we investigated the effects of acute (7 days) glucose-induced hyperglycemia and sodium acetoacetate (NaAcAc) or ammonium chloride (NH4Cl) induced acidosis on the level of indolamines (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)) as well as PKC-alpha expression/activity in discrete areas of rat brain. Glucose-induced (500 mg/kg, bw) hyperglycemic ( approximately 249 mg%) rats showed significant (p<0.05) increase in 5-HT levels in mid brain (MB), pons medulla (PM) and cerebellum (CB), respectively. 5-HIAA level increased in hippocampus (HC) (p<0.05) as compared to control. The rats treated with sodium acetoacetate (NaAcAc) for 7 days (60 mg/kg, bw) showed significant decrease (p<0.05) of 5-HT level in hypothalamus (HT). Whereas, the 5-HIAA level increased in MB (p<0.05). Similarly, the PKC-alpha expression as well as the enzyme activity showed significant increase in HC, MB, PM and CB under glucose-induced hyperglycemia and that changes correlated the changes of indolamines, suggesting that the hyperglycemia may be the major metabolic disorder in diabetic complications.

A short-term diabetes induced changes of catecholamines and p38-MAPK in discrete areas of rat brain.

Chronic diabetes is associated with the alteration of second messengers and CNS disorders. We have recently identified that protein kinases (CaMKII and PKC-alpha) and brain neurotransmitters are altered during diabetes as well as in hyperglycemic and acidotic conditions. In this study, we investigated the effects of acute diabetes on the levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and p38-Mitogen-Activated Protein Kinase (p38-MAPK) in striatum (ST), hippocampus (HC), hypothalamus (HT), midbrain (MB), pons medulla (PM), cerebellum (CB) and cerebral cortex (CCX). Alloxan (45 mg/kg) diabetic untreated rats that showed hyperglycemia (>260 mg%), revealed significant increases of DA level in ST (1.5 fold), HC (2.2 fold) and PM (2.0 fold) and the E level also found to be increased significantly in HT (2.4 fold), whereas the NE level was decreased in CB (0.5 fold), after 7 days of diabetes. Immunoblotting study of p38-MAPK expression under identical conditions showed significant alterations in ST, HC, HT and PM (p<0.05) correlated with the changes of catecholamines (DA and E). On the other hand, the above changes were reversed in insulin-treated diabetic rats maintained under normal glucose level (80 -110 mg %). These results suggest that p38-MAPK may regulate the rate of either the synthesis or release of DA and E in corresponding brain areas, but not NE, under these conditions.

Involvement of Ca2+/calmodulin-dependent protein kinase II in the modulation of indolamines in diabetic and hyperglycemic rats.

Hyperglycemia and acidosis are the key factors in diabetic complications. It has been shown that acute or chronic diabetes alters serotonin levels in brain. However, the mechanism of hyperglycemia- or acidosis-induced changes in serotonin levels remains poorly understood. Because Ca2+-dependent protein kinases play a major role in the regulation of serotonin synthesis and release, we investigated the effect of diabetes, hyperglycemia, and acidosis on the level of indolamines [5-hydroxytryptamine (5-HT) and/or 5-hydroxyindoleacetic acid (5-HIAA)] and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) enzyme activity or protein expression in different brain regions. Alloxan-induced (45 mg/kg bw) diabetic rats (30 days) showed increased level of 5-HT in striatum (ST; 183%), midbrain (MB; 199%), pons medulla (PM; 151%), cerebellum (CB; 214%), and cerebral cortex (CCX; 162%) compared with control (P < 0.05), and these changes were reversed after insulin administration. Rats treated with glucose (500 mg/kg bw) for 30 days showed a 146%, 183%, 208%, and 177% (P < 0.05) increase in 5-HT levels in ST, PM, CB, and CCX, respectively. 5-HIAA level increased in hippocampus (HC; 172%) and in MB (145%; P < 0.05). In addition, rats treated with sodium acetoacetate (NaAcAc) for 30 days (60 mg/kg bw) showed significant increases (P < 0.05) of 5-HT level in ST (152%) and MB (174%). However, the levels of 5-HIAA increased only in MB (151%, P < 0.05). Rats treated with NH4Cl, which induced acidosis (150 mg/kg bw), showed an increased level of 5-HT only in HC (165%, P < 0.05). The increased activity and protein expression of CaMKII in ST, MB, PM, CB, and CCX under diabetic conditions were correlated with the levels of indolamines changes during diabetic, hyperglycemic, or acidotic conditions. These results suggest that CaMKII may be involved in the regulation of indolamines in diabetic animals.

PKC-alpha mediated alterations of indoleamine contents in diabetic rat brain.

We previously have reported that acute or chronic diabetes in animals resulted in altered neurotransmitter levels. In this study, we investigated the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete areas of brain viz. striatum (ST), hippocampus (HC), hypothalamus (HT), midbrain (MB), pons medulla (PM), cerebellum (CB) and cerebral cortex (CCX) of control, untreated diabetic and insulin treated diabetic rats after 30 days. Alloxan (45 mg/kg) diabetic untreated rats, which showed hyperglycemia (>250 mg%), revealed significant increases of 5-HT level in ST, MB, PM, CB and CCX and the 5-HIAA level found to be increased significantly in ST, HC and MB. Whereas the insulin treated rats, which was maintained under normal glucose level (80-110 mg%), showed no significant changes in any of the areas studied. The expressions of PKC-alpha studied by immunoblotting also showed significant changes in ST, HC, MB, PM, CB and CCX that is identical to the changes of both 5-HT and 5-HIAA under similar condition, suggesting that the PKC-alpha may regulate the synthesis and release of indoleamines in diabetic animals.

An experimental analysis of the catecholamines in hyperglycemia and acidosis induced rat brain.

Hyperglycemia and acidosis are the hallmark of diabetes. Since these factors play an important role in the diabetic complications, we have studied the brain catecholamine levels in hyperglycemic and acidotic conditions per se. Experimentally induced hyperglycemia and acidosis are accompanied by significant alterations in the catecholamine levels in discrete areas of the brain. We and others have shown that chronic or acute diabetes in animals as well as in human results in altered neurotransmitter levels. In the present study, hyperglycemia maintained by daily external administration of glucose for thirty days showed increased level of dopamine in striatum and hippocampus, elevation of norepinephrine in hippocampus, and increased level of epinephrine in hypothalamus, midbrain and pons medulla. The ammonium chloride induced acidosis demonstrated significant elevation of dopamine in midbrain and significant increase of norepinephrine in hypothalamus and midbrain, and increased level of epinephrine in hypothalamus, pons medulla and cerebral cortex. On the other hand, sodium acetoacetate induced acidosis did not show any significant change in the level of catecholamines in any of the areas studied. In conclusion, the changes in catecholamine levels observed in experimentally induced hyperglycemic as well as in acidotic conditions are closely related to the changes observed in spontaneous or alloxan or streptozotocin diabetic animals, thereby suggesting that these conditions may be responsible for the changes observed in diabetic animals.

Reticuloendothelial function in acute noise stress.

Wistar strain albino rats of either sex were subjected to acute noise stress (3000 Hz at > 97 dB) for 30 minutes. Carbon clearance test was conducted in noise stressed animals immediately after the stress period. Significant (P < 0.001) increase of the clearance constant K was observed in stressed animals compared to the controls, indicating increased phagocytic activity of the reticuloendothelial system.

Effect of acute heat stress on certain immunological parameters in albino rats.

The effect of acute heat stress on certain immunological parameters were studied in male albino rats. The test rats were exposed to an ambient temperature of 40 degrees celsius for 30 minutes and sacrificed immediately. Total WBC count, Differential count, Phagocytic index, NBT reduction, organ weight body weight ratio of spleen, thymus, and popliteal lymph nodes, and soluble immune complex levels were measured in control group and the heat stressed animals. The heat stressed animals show decrease in total WBC count, and neutrophilia, eosinophilia, and lymphocytopenia. The phagocytic index showed a significant increase whereas the avidity index showed a decrease from the control value. NBT reduction was also significant. The soluble immune complex level was not altered. The heat stressed animals showed a decrease in the thymus and spleen weight/body weight ratio while the lymph node/body weight ratio showed an increase compared to the control animals.

Certain immunological parameters in subacute cold stress.

The effect of subacute cold swimming stress on the immune system of albino rats was investigated. Subacute cold stressed animals showed an increase in total WBC count, eosinophils and basophils. Phagocytic index and avidity index were also increased indicating hyperactive phagocytic process. On the other hand NBT reduction and soluble immune complex levels decreased significantly in stressed animals. There were no significant changes in the weight of the lymphoid organs.

Studies on monoamine levels in rat myocardium in different stresses.

Albino rats were exposed to isolation, haemorrhagic, and psychic stress. The myocardial norepinephrine (NE), epinephrine (E), dopamine (DA), 5-hydroxytryptamine (5HT) and 5-hydroxy indole acetic acid (5HIAA) were quantitatively estimated at varying periods of time. The results indicate that 5HT, E, and DA are the common denominators in various types of stress and show similar qualitative changes in all the stresses studied whereas norepinephrine shows both quantitative and qualitative differences in the various stresses studied indicating thereby a differential modulatory mechanisms operating for the release of noradrenaline.

Effect of flickering light stress on certain biochemical parameters in rats.

The acute effects of flickering light of 80 Lux intensity for thirty minutes duration, on plasma corticosterone, total serum cholesterol, serum triglycerides, serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) levels were studied in albino rats. Statistically significant increase was observed in the corticosterone, cholesterol, SGOT and SGPT, while a marked reduction was seen in the serum triglyceride level, indicating that the flickering light is a potent stressor to these animals causing alterations in the biochemical parameters studied.

Biochemical changes in acute noise stress in rats.

The effects of acute auditory stress on certain biochemical parameters like blood corticosterone, total cholesterol, triglyceride, Serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) were studied in albino rats. A significant increase was observed in the blood level of corticosterone, total cholesterol, SGOT and SGPT while a marked reduction was noticed in the Sr. triglyceride level. These data indicate that noise could be a potent stressor and cause disturbances in the biochemical parameters of the body. It is presumed that most of the effects are indirect, being manifested through the activation of autonomic nervous system which liberates catecholamines and hypothalamo pituitary adrenal axis responsible for the liberation of corticosteroids.

Influence of isolation stress on monoamine levels in discrete regions of the rat brain correlated with behaviour.

Various forms of stressful stimuli have been shown to affect brain catecholamine (CA) and indoleamine (IA) levels, although the literature contains some conflicting views. Changes in monoamine levels were also found to accompany the behavioural changes in animals. In the present study an attempt was made to correlate the behavioural changes with the monoamine level in discrete regions of rat brain after different periods of isolation stress. The results clearly indicate that not only the central norepinephrine and dopamine neurons involved in the expression of aggressive behaviour after isolation stress but also the serotoninergic neurons might take part.