Monoamine transporter gene expression in the central nervous system in diabetes mellitus.
Diabetic animals exhibit altered neurotransmission in brain monoaminergic systems. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline, and serotonin transporter (DA-T, NA-T, and 5-HT-T, respectively) mRNAs in the brains of alloxan- and streptozotocin-diabetic rats. The expression of DA-T mRNA is decreased in 1- (-11%) and 4- (-17%) week alloxan-diabetic and 4- (-9%) and 8- (-20%) week streptozotocin-diabetic rats in the ventral medial bundle. The expression of NA-T mRNA is decreased in the locus coeruleus of 8- (-26%) week streptozotocin-diabetic rats, in the noradrenergic A1 cell group of 4- (-27%) week alloxan- and 8- (-25%) week streptozotocin-diabetic rats, and in the noradrenergic A2 cell group of 1- (-21%) and 4- (-28%) week alloxan-diabetic and 4- (-27%) and 8- (-25%) week streptozotocin-diabetic animals. The expression of 5-HT-T mRNA in the dorsal raphe nucleus is increased in 1- (+14%) and 4- (+44%) week alloxan- and 4- (+28%) and 8- (+44%) week streptozotocin-diabetic rats. The expression of each of the three monoamine transporter genes may be differentially regulated in diabetes and dependent on the duration of diabetes. Altered monoamine transporter gene expression may possibly contribute to the observed dysfunctions in brain monoamine transmission in chronic diabetes.
Petrisić
M S
MS
Croatian Brain Research Institute and Department of Pharmacology, Medical School, University of Zagreb, Croatia.
Augood
S J
SJ
Bicknell
R J
RJ
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000166:cytology; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000737:chemistry / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D009638:Norepinephrine / Q000502:physiology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D009638:Norepinephrine