title: Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight.
abstract: After synaptic release, glutamate is taken up by the nerve terminal via a plasma membrane-associated protein termed excitatory amino acid transporter 3 (EAAT3). Following entry into the nerve terminal, glutamate is pumped into synaptic vesicles by a vesicular transport system. Three different vesicular glutamate transporter proteins (VGLUT1-3) representing unique markers for glutamatergic neurons were recently characterized. The presence of EAAT3, glutaminase and VGLUT1-3 was examined in mouse, rat and rabbit species at mRNA and protein levels in hypothalamic neurons which are involved in the regulation of body weight using in situ hybridization and immunohistochemistry. EAAT3 and glutaminase mRNAs were demonstrated in all parts of the arcuate nucleus in the dorsomedial and ventromedial hypothalamic nuclei and lateral hypothalamic area. VGLUT1 mRNA was present in the magnocellular lateral hypothalamic nucleus. VGLUT2 mRNA was demonstrated in a subpopulation of neurons in the arcuate nucleus and in the ventromedial and dorsomedial hypothalamic nuclei and lateral hypothalamic area. Few VGLUT3 mRNA expressing neurons were scattered throughout the medial and lateral hypothalamus. EAAT3-like immunoreactivity (-li) was demonstrated in glutamate, neuropeptide Y (NPY), agouti-related peptide (AGRP), pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), melanin-concentrating hormone and orexin-immunoreactive (-ir) neurons. VGLUT2-li could only be demonstrated in POMC- and CART-ir neurons of the ventrolateral arcuate nucleus. The results show that key neurons involved in regulation of energy balance are glutamatergic and/or densely innervated by glutamatergic nerve terminals. Whereas orexigenic NPY/AGRP neurons situated in the ventromedial part of the arcuate nucleus are mainly GABAergic, it is shown that several anorexigenic POMC/CART neurons of the ventromedial arcuate nucleus are most likely glutamatergic [corrected].
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, B3, 5th Floor, Room 514, SE-171 77 Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Collin
authors.forename: Matilda
authors.initials: M
authors.lastname: Bäckberg
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Ovesjö
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fisone
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Fumino
authors.initials: F
authors.lastname: Fujiyama
authors.forename: Björn
authors.initials: B
authors.lastname: Meister
mesh_terms: D054369:Agouti-Related Protein; D027322:Amino Acid Transport System X-AG / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003510:Cyclohexanes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D005972:Glutaminase / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D007150:Immunohistochemistry / Q000295:instrumentation / Q000379:methods; D017403:In Situ Hybridization / Q000401:mortality; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D013045:Species Specificity; D027981:Symporters / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054369:Agouti-Related Protein; D027322:Amino Acid Transport System X-AG; D026922:Amino Acid Transport Systems, Acidic; D002352:Carrier Proteins; D003510:Cyclohexanes; D004268:DNA-Binding Proteins; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D011506:Proteins; D012333:RNA, Messenger; C460879:SLC17A8 protein, human; D050796:STAT3 Transcription Factor; C493477:Slc17a6 protein, mouse; C493475:Slc17a6 protein, rat; C493465:Slc17a7 protein, mouse; C493466:Slc17a7 protein, rat; C493399:Slc1a1 protein, mouse; C493398:Slc1a1 protein, rat; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D027981:Symporters; D015534:Trans-Activators; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin; C473568:3-methyl-2-cyclohexen-1-one; D005972:Glutaminase