Serotonergic Neurons Are Targets for Leptin in the Monkey1
Patricia D. Finn2,3,
Matthew J. Cunningham3,
Diana G. Rickard,
Donald K. Clifton and
Robert A. Steiner
Departments of Physiology and Biophysics (P.D.F., D.G.R., R.A.S.)
and Obstetrics and Gynecology (D.K.C., R.A.S.), Graduate Program in
Neurobiology and Behavior (M.J.C.), and the Specialized Cooperative
Centers Program in Reproduction Research (D.K.C., R.A.S.), University
of Washington, Seattle, Washington 98195
Address all correspondence and requests for reprints to: Dr. Robert A. Steiner, Department of Physiology and Biophysics, Box 357290, University of Washington, Seattle, Washington 98195-7290. E-mail:
steiner{at}u.washington.edu
Leptin is a secretory product of adipocytes that has been shownto
affect food intake, metabolism, and reproduction. One siteof leptin’s
action is the central nervous system, wherethe leptin receptor (Ob-R)
messenger ribonucleic acid (mRNA)and protein are expressed in discrete
areas. In both the ratand monkey, Ob-R mRNA has been localized in the
Raphe nucleiof the brainstem. Neurons in the Raphe nuclei are the
primarysource of serotonin in the brain. Serotonergic pathways
influenceboth feeding and reproduction, and these cells are plausible
directtargets for leptin’s action. We used double label in
situhybridization and computerized image analysis to determine
whetherserotonergic neurons in the brainstem of the female pigtailed
macaque(Macaca nemestrina) express Ob-R mRNA. We
observed that manycells in the Raphe nuclei express serotonin
transporter mRNA,a marker of serotonergic cells, and Ob-R mRNA. Based
on quantitativeanalysis, the highest number of cells that express both
serotonintransporter and Ob-R mRNAs were found in the caudal dorsal
Rapheand median Raphe nuclei; fewer double labeled cells were situated
inthe caudal linear nucleus and rostral median Raphe, whereasdouble
labeled cells occurred infrequently in the rostral dorsalRaphe. These
observations suggest that leptin may act on serotonergiccells to
mediate some of its effects on ingestive behavior,metabolism, and
reproduction.
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