Differential expression of monoamine oxidase A, serotonin transporter, tyrosine hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food deprivation.
The Anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3-4 weeks. We have found serotonin (5HT) hyperinnervation in the anx brain; altered noradrenergic (NE) innervation may also mediate eating disorders. We examined the expression of synthetic or catabolic monoamine enzyme genes in brainstem nuclei: serotonin transporter (5HTT) and monoamine oxidase A (MAOA) in the raphe nuclei (RN), and MAOA, norepinephrine transporter (NET), and tyrosine hydroxylase (TH) in the locus ceruleus (LC). We compared 3-week old anx with control and 24-h food-deprived wildtype littermates using in situ hybridization to measure mRNA levels by quantitative autoradiography. The anx mutation was correlated with decreased MAOA mRNA in the LC (but not RN), decreased 5HTT mRNA in the RN, and a trend towards lower NET mRNA in the LC. Food deprivation decreased MAOA mRNA in the LC (but not RN), increased TH mRNA in the LC, and did not alter NET or 5HTT mRNA levels. Thus, the effect of the anx mutation on MAOA expression in the LC paralleled the effect of food-deprivation, but the anx mutation and food-deprivation had differential effects on the expression of TH, NET, and 5HTT genes. Decreased 5HTT expression in the anx RN is consistent with upregulation of serotonergic neurotransmission that may accompany 5HT hyperinnervation. Central NE levels or innervation may be altered in anx mice by decreased expression of NET and MAOA and a lack of TH upregulation induced by food deprivation as in wild-type mice.
Jahng
J W
JW
Laboratory of Molecular Neurobiology, Burke Medical Research Institute, Department of Neurology and Neuroscience, Cornell University Medical College, White Plains, NY 10605, USA.
Houpt
T A
TA
Joh
T H
TH
Son
J H
JH
D000818:Animals; D000855:Anorexia / Q000201:enzymology* / Q000235:genetics*; D001345:Autoradiography; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis*; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D051379:Mice; D008818:Mice, Neurologic Mutants; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D002352:Carrier 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; C493228:Slc6a2 protein, mouse; C493231:Slc6a4 protein, mouse; D027981:Symporters; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase