title: Distribution and neurochemical characterization of protein kinase C-theta and -delta in the rodent hypothalamus.
abstract: PKC-theta (PKC-θ), a member of the novel protein kinase C family (nPKC), regulates a wide variety of functions in the periphery. However, its presence and role in the CNS has remained largely unknown. Recently, we demonstrated the presence of PKC-θ in the arcuate hypothalamic nucleus (ARC) and knockdown of PKC-θ from the ARC protected mice from developing diet-induced obesity. Another isoform of the nPKC group, PKC-delta (PKC-δ), is expressed in several non-hypothalamic brain sites including the thalamus and hippocampus. Although PKC-δ has been implicated in regulating hypothalamic glucose homeostasis, its distribution in the hypothalamus has not previously been described. In the current study, we used immunohistochemistry to examine the distribution of PKC-θ and -δ immunoreactivity in rat and mouse hypothalamus. We found PKC-θ immunoreactive neurons in several hypothalamic nuclei including the ARC, lateral hypothalamic area, perifornical area and tuberomammillary nucleus. PKC-δ immunoreactive neurons were found in the paraventricular and supraoptic nuclei. Double-label immunohistochemisty in mice expressing green fluorescent protein either with the long form of leptin receptor (LepR-b) or in orexin (ORX) neurons indicated that PKC-θ is highly colocalized in lateral hypothalamic ORX neurons but not in lateral hypothalamic LepR-b neurons. Double-label immunohistochemistry in oxytocin-enhanced yellow fluorescent protein mice or arginine vasopressin-enhanced green fluorescent protein (AVP-EGFP) transgenic rats revealed a high degree of colocalization of PKC-δ within paraventricular and supraoptic oxytocin neurons but not the vasopressinergic neurons. We conclude that PKC-θ and -δ are expressed in different hypothalamic neuronal populations.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8854, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Irani
authors.forename: J
authors.initials: J
authors.lastname: Donato
authors.forename: D P
authors.initials: DP
authors.lastname: Olson
authors.forename: B B
authors.initials: BB
authors.lastname: Lowell
authors.forename: T C
authors.initials: TC
authors.lastname: Sacktor
authors.forename: M E
authors.initials: ME
authors.lastname: Reyland
authors.forename: K P
authors.initials: KP
authors.lastname: Tolson
authors.forename: A R
authors.initials: AR
authors.lastname: Zinn
authors.forename: Y
authors.initials: Y
authors.lastname: Ueta
authors.forename: I
authors.initials: I
authors.lastname: Sakata
authors.forename: J M
authors.initials: JM
authors.lastname: Zigman
authors.forename: C F
authors.initials: CF
authors.lastname: Elias
authors.forename: D J
authors.initials: DJ
authors.lastname: Clegg
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000378:metabolism; D007031:Hypothalamus / Q000201:enzymology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D051381:Rats; D020318:Rats, Long-Evans; D054411:Receptors, Leptin / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D054411:Receptors, Leptin; D001127:Arginine Vasopressin; D010121:Oxytocin; C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; C489593:Prkcq protein, mouse; C489591:Prkcq protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta; D006640:Histidine Decarboxylase