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Involvement of Ca 2+ /calmodulin‐dependent protein kinase II in the modulation of indolamines in diabetic and hyperglycemic rats
Author(s) -
Ramakrishnan R.,
Prabhakaran K.,
Jayakumar A.R.,
Gunasekaran P.,
Sheeladevi R.,
Suthanthirarajan N.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20499
Subject(s) - endocrinology , medicine , serotonin , chemistry , insulin , diabetes mellitus , receptor
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 Ca 2+ ‐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 NH 4 Cl, 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. © 2005 Wiley‐Liss, Inc.