Diabetes causes differential changes in CNS noradrenergic and dopaminergic neurons in the rat: a molecular study.
We have previously reported that chronic elevation of insulin in the CNS of rats results in opposing changes of the mRNA expression for the norepinephrine transporter (NET; decreased) and the dopamine transporter (DAT; increased). In the present study we tested the hypothesis that a chronic depletion of insulin would result in opposite changes of NET and DAT mRNA expression, from those observed with chronic elevation of insulin. Rats were treated with streptozotocin to produce hypoinsulinemic diabetes. One week later, steady state levels of mRNA were measured by in situ hybridization for NET in the locus coeruleus (LC) and for DAT in the ventral tegmental area/substantia nigra compacta (VTA/SNc). The mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA synthesis, was measured in these same brain regions. In the diabetic animals, NET mRNA was significantly elevated (159 +/- 22% of average control level) while DAT mRNA was non-significantly decreased (78 +/- 9% of average control level). Additionally, TH mRNA was significantly altered in both the LC (131 +/- 11% of average control level) and VTA/SNc (79 +/- 5% of average control level). We conclude that endogenous insulin is one physiological regulator of the synthesis and re-uptake of NE and DA in the CNS.
Figlewicz
D P
DP
Department of Psychology, University of Washington, Seattle 98195, USA.
Brot
M D
MD
McCall
A L
AL
Szot
P
P
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D027981:Symporters; D013681:Tegmentum Mesencephali / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
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; C493226:Slc6a2 protein, rat; C493216:Slc6a3 protein, rat; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine