title: Pharmacological and Morphological Evidence of AMPK-Mediated Energy Sensing in the Lower Brain Stem Ependymocytes to Control Reproduction in Female Rodents.
abstract: Ependymocytes are one of the energy-sensing cells that regulate animal reproduction through their responsiveness to changes in extracellular glucose levels and the expression of pancreatic-type glucokinase and glucose transporter 2, which play a critical role in sensing blood glucose levels in pancreatic β-cells. Molecular mechanisms underlying glucose sensing in the ependymocytes remain poorly understood. The AMP-activated protein kinase (AMPK), a serine/threonine kinase highly conserved in all eukaryotic cells, has been suggested to be an intracellular fuel gauge that detects cellular energy status. The present study aims to clarify the role AMPK of the lower brainstem ependymocytes has in sensing glucose levels to regulate reproductive functions. First, we will show that administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, into the 4th ventricle suppressed pulsatile LH release in female rats. Second, we will demonstrate the presence of AMPK catalytic subunit immunoreactivities in the rat lower brainstem ependymocytes. Third, transgenic mice were generated to visualize the ependymocytes with Venus, a green fluorescent protein, expressed under the control of the mouse vimentin promoter for further in vitro study. The Venus-labeled ependymocytes taken from the lower brainstem of transgenic mice revealed that AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, increased in vitro intracellular calcium concentrations. Taken together, malnutrition-induced AMPK activation of ependymocytes of the lower brainstem might be involved in suppression of GnRH/LH release and then gonadal activities.
authors.affiliation: Graduate School of Bioagricultural Sciences (S.M., C.D., K.I., T.G., N.I., Y.U., H.T.), Nagoya University, Nagoya, Aichi 464-8601, Japan; Center for Genetic Analysis of Behavior (M.S., M.H.), National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan; and Veterinary Medical Sciences (K.-i.M.), University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Minabe
authors.forename: Chikaya
authors.initials: C
authors.lastname: Deura
authors.forename: Kana
authors.initials: K
authors.lastname: Ikegami
authors.forename: Teppei
authors.initials: T
authors.lastname: Goto
authors.forename: Makoto
authors.initials: M
authors.lastname: Sanbo
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoue
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: Kei-Ichiro
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D012263:Ribonucleosides / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D055372:AMP-Activated Protein Kinases
references.citation: Am J Physiol. 1999 May;276(5 Pt 2):R1223-31
references.pmid: 10233011
references.citation: Endocrinology. 2005 Jan;146(1):3-10
references.pmid: 15375032
references.citation: Am J Physiol. 1988 Aug;255(2 Pt 2):R200-4
references.pmid: 3044143
references.citation: Gene. 1995 Dec 12;166(2):281-6
references.pmid: 8543176
references.citation: Neurosci Biobehav Rev. 1992 Summer;16(2):235-72
references.pmid: 1630733
references.citation: Endocrinology. 2003 Oct;144(10):4325-31
references.pmid: 12960045
references.citation: Int J Eat Disord. 2007 Jul;40(5):424-34
references.pmid: 17497704
references.citation: J Neurochem. 2003 Aug;86(3):709-24
references.pmid: 12859684
references.citation: Horm Metab Res. 1990 May;22(5):269-72
references.pmid: 2347540
references.citation: J Physiol Sci. 2011 Mar;61(2):103-13
references.pmid: 21234734
references.citation: Am J Physiol Regul Integr Comp Physiol. 2014 Feb 15;306(4):R257-64
references.pmid: 24381177
references.citation: Biochem J. 2003 May 1;371(Pt 3):761-74
references.pmid: 12589707
references.citation: Diabetes. 2011 Feb;60(2):436-42
references.pmid: 21270255
references.citation: Methods Mol Biol. 2014;1170:113-44
references.pmid: 24906312
references.citation: Endocrinology. 2004 May;145(5):2507-15
references.pmid: 14962992
references.citation: J Physiol. 2011 May 1;589(Pt 9):2275-86
references.pmid: 21486800
references.citation: Nature. 2004 Apr 1;428(6982):569-74
references.pmid: 15058305
references.citation: J Reprod Dev. 2011 Oct;57(5):660-4
references.pmid: 21804302
references.citation: Endocrinology. 1996 Apr;137(4):1166-70
references.pmid: 8625885
references.citation: J Endocrinol. 1989 May;121(2):277-83
references.pmid: 2754361
references.citation: Am J Physiol. 1982 Oct;243(4):E310-8
references.pmid: 6889816
references.citation: Diabetes. 2001 Jan;50(1):1-11
references.pmid: 11147773
references.citation: Diabetologia. 2007 Jan;50(1):168-77
references.pmid: 17093945
references.citation: Anim Reprod Sci. 2000 Jul 2;60-61:449-57
references.pmid: 10844215
references.citation: J Endocrinol. 1991 Jun;129(3):321-8
references.pmid: 2066689
references.citation: Nature. 2007 Sep 27;449(7161):496-500
references.pmid: 17851531
references.citation: Science. 1981 Jul 24;213(4506):451-2
references.pmid: 6264602
references.citation: J Anim Sci. 1987 Mar;64(3):805-15
references.pmid: 3571004
references.citation: Cell Metab. 2008 May;7(5):389-99
references.pmid: 18460330
references.citation: Am J Anat. 1966 Nov;119(3):479-97
references.pmid: 5972733
references.citation: Glia. 2012 Jan;60(1):53-68
references.pmid: 21987367
references.citation: Nat Cell Biol. 2011 Sep;13(9):1016-23
references.pmid: 21892142
references.citation: J Neurochem. 2009 Oct;111(2):315-20
references.pmid: 19686385
references.citation: J Physiol. 1985 May;362:245-60
references.pmid: 4020688
references.citation: Nature. 1969 Apr 19;222(5190):282-4
references.pmid: 5778398
references.citation: J Comp Neurol. 2001 Apr 2;432(2):197-216
references.pmid: 11241386
references.citation: Endocrinology. 1985 Jan;116(1):375-81
references.pmid: 3964750
references.citation: Endocrinology. 1996 Apr;137(4):1171-6
references.pmid: 8625886
references.citation: Annu Rev Physiol. 2007;69:377-400
references.pmid: 17009929
references.citation: Neuron. 2014 Feb 19;81(4):728-39
references.pmid: 24559669
references.citation: ASN Neuro. 2010;2(3):e00035
references.pmid: 20531973
references.citation: FEBS Lett. 2003 Jul 3;546(1):113-20
references.pmid: 12829246
references.citation: Am J Clin Nutr. 1992 Jan;55(1 Suppl):278S-282S
references.pmid: 1370249
references.citation: J Reprod Dev. 2004 Dec;50(6):697-704
references.pmid: 15647622
references.citation: Trends Mol Med. 2008 Dec;14(12):539-49
references.pmid: 18977694
references.citation: J Reprod Dev. 2011 Jun;57(3):379-84
references.pmid: 21358145
references.citation: Science. 1964 Jan 31;143(3605):484-5
references.pmid: 14080319
references.citation: J Reprod Dev. 2004 Jun;50(3):279-85
references.pmid: 15226592
references.citation: Acta Neuropathol. 2010 Jan;119(1):55-73
references.pmid: 20024659
references.citation: Domest Anim Endocrinol. 2003 Jul;25(1):109-20
references.pmid: 12963104
references.citation: Endocrinology. 2009 May;150(5):2175-82
references.pmid: 19116341
references.citation: Endocrinology. 1993 May;132(5):1890-7
references.pmid: 8477642
references.citation: J Anat. 1989 Aug;165:87-100
references.pmid: 17103628
references.citation: Biochem Biophys Res Commun. 2008 Feb 8;366(2):388-92
references.pmid: 18068666
references.citation: Endocrinology. 2000 Jan;141(1):375-84
references.pmid: 10614660