Alteration of Monoamines Processing in the Brain of db/db Diabetic Mice
Abstract Number: 982-P
Authors: AJAYKUMAR N. SHARMA, KHALID M. ELASED, JAMES B. LUCOT
Institutions: Dayton, OH
Results: Recent clinical data indicate neuropsychological disturbances in type-2 diabetics. The underlying mechanisms by which diabetes influences these behaviors remain to be elucidated. Classic theories of major neuropsychological disorders such as depression, psychosis and Parkinsonism suggest abnormal changes in monoamine concentrations like dopamine (DA), serotonin (5-HT), norepinephrine (NE) and their metabolites in specific brain regions. Our recent data have shown the presence of depression and psychosis-like symptoms in db/db diabetic mice. The present study was designed to investigate possible alterations in concentrations of monoamines and their metabolites in db/db mouse brain. The db/db mouse brain frontal cortex (FC), amygdala, caudate, hippocampus, hypothalamus and brain stem (BS) were analyzed by reverse-phase high performance liquid chromatography (HPLC) for concentrations of monoamines DA, 5-HT, NE and DA metabolites: homovanilic acids (HVA) and dihydroxyphenylacetic acid (DOPAC). The ratios of these metabolites and parent neurotransmitter DA: HVA/DA and DOPAC/DA were calculated as an index of neurotransmitter usage. There was increased HVA/DA in FC, decreased HVA/DA and DOPAC/DA in amygdala and caudate and no change in these ratios in hippocampus, hypothalamus and BS of db/db mice. Increases in 5-HT concentrations were seen in FC, amygdala, caudate and BS. NE concentrations were elevated in FC, hypothalamus and BS. Many changes were related to the behavioral abnormalities observed in these mice. This is the first evidence of altered DA processing pattern in db/db mouse brain which may help to improve our understanding of type-2 diabetes-induced neuropsychological disorders.