title: Bidirectional neuro-glial signaling modalities in the hypothalamus: role in neurohumoral regulation.
abstract: Maintenance of bodily homeostasis requires concerted interactions between the neuroendocrine and the autonomic nervous systems, which generate adaptive neurohumoral outflows in response to a variety of sensory inputs. Moreover, an exacerbated neurohumoral activation is recognized to be a critical component in numerous disease conditions, including hypertension, heart failure, stress, and the metabolic syndrome. Thus, the study of neurohumoral regulation in the brain is of critical physiological and pathological relevance. Most of the work in the field over the last decades has been centered on elucidating neuronal mechanisms and pathways involved in neurohumoral control. More recently however, it has become increasingly clear that non-neuronal cell types, particularly astrocytes and microglial cells, actively participate in information processing in areas of the brain involved in neuroendocrine and autonomic control. Thus, in this work, we review recent advances in our understanding of neuro-glial interactions within the hypothalamic supraoptic and paraventricular nuclei, and their impact on neurohumoral integration in these nuclei. Major topics reviewed include anatomical and functional properties of the neuro-glial microenvironment, neuron-to-astrocyte signaling, gliotransmitters, and astrocyte regulation of signaling molecules in the extracellular space. We aimed in this review to highlight the importance of neuro-glial bidirectional interactions in information processing within major hypothalamic networks involved in neurohumoral integration.
authors: Department of Physiology, Georgia Health Sciences University, Augusta, GA 30912, USA. jstern@georgiahealth.edu
authors: J E
authors: JE
authors: Stern
authors: J A
authors: JA
authors: Filosa
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000502:physiology
references: Am J Physiol Endocrinol Metab. 2004 Apr;286(4):E535-41
references: 14665445
references: Science. 1989 Nov 10;246(4931):815-8
references: 2573153
references: J Physiol. 2006 Jun 15;573(Pt 3):711-21
references: 16613872
references: Eur J Neurosci. 2003 Jul;18(1):206-14
references: 12859353
references: J Physiol. 2007 Jul 15;582(Pt 2):539-51
references: 17495040
references: Am J Physiol Regul Integr Comp Physiol. 2001 Jun;280(6):R1815-22
references: 11353687
references: Prog Biophys Mol Biol. 2004 Feb-Apr;84(2-3):197-215
references: 14769436
references: J Physiol. 1985 Dec;369:45-60
references: 4093889
references: Ann N Y Acad Sci. 2001 Jun;940:444-53
references: 11458700
references: J Neuroendocrinol. 2004 Sep;16(9):727-39
references: 15344911
references: Prog Brain Res. 2008;170:109-17
references: 18655876
references: Neuron. 2007 May 24;54(4):497-500
references: 17521561
references: Brain Res. 1991 Oct 4;561(1):151-6
references: 1797341
references: J Neurochem. 2009 Apr;109(2):656-69
references: 19245663
references: Brain Res. 1976 Nov 26;117(2):305-12
references: 62600
references: J Physiol. 2001 Nov 15;537(Pt 1):161-77
references: 11711570
references: Endocrinology. 1993 Feb;132(2):530-3
references: 8425473
references: J Physiol. 1995 Dec 1;489 ( Pt 2):567-77
references: 8847648
references: Prog Neurobiol. 2000 Oct;62(2):113-34
references: 10828380
references: Neuron. 2008 Sep 25;59(6):932-46
references: 18817732
references: Annu Rev Neurosci. 1983;6:269-324
references: 6132586
references: Neuroscience. 2000;96(4):807-15
references: 10727798
references: Neuropharmacology. 2000 Jun 8;39(8):1337-56
references: 10818251
references: Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R254-60
references: 19907001
references: Science. 1993 Jan 15;259(5093):381-4
references: 7678352
references: J Physiol. 2007 Apr 15;580(Pt. 2):373-83
references: 17185337
references: Am J Physiol Regul Integr Comp Physiol. 2006 May;290(5):R1208-15
references: 16357097
references: Curr Alzheimer Res. 2009 Oct;6(5):424-30
references: 19874266
references: Prog Clin Biol Res. 1990;351:369-76
references: 2236143
references: Neuron. 1996 Mar;16(3):675-86
references: 8785064
references: Nat Neurosci. 1998 Dec;1(8):683-92
references: 10196584
references: Brain Res Brain Res Rev. 1999 Jul;30(1):52-65
references: 10407125
references: Prog Brain Res. 2008;170:119-28
references: 18655877
references: Brain Res. 1989 Apr 10;484(1-2):361-6
references: 2713693
references: Mol Pharmacol. 1995 Nov;48(5):841-8
references: 7476914
references: J Auton Nerv Syst. 1988 Dec;25(2-3):135-40
references: 3235776
references: Neurobiol Dis. 2008 Jul;31(1):58-73
references: 18499466
references: Brain Res. 1998 Mar 30;788(1-2):43-8
references: 9554947
references: Neuroscience. 1994 Nov;63(1):223-31
references: 7534881
references: Am J Physiol. 1998 May;274(5):R1345-52
references: 9612401
references: Nature. 2006 Apr 20;440(7087):1054-9
references: 16547515
references: Am J Physiol Endocrinol Metab. 2001 Feb;280(2):E349-56
references: 11158940
references: Neurochem Int. 2010 Nov;57(4):451-9
references: 20156504
references: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5364-8
references: 2052613
references: Nat Rev Neurosci. 2005 Aug;6(8):626-40
references: 16025096
references: Brain Res. 2002 Jan 18;925(1):42-54
references: 11755899
references: Nat Rev Neurosci. 2008 Jul;9(7):519-31
references: 18509340
references: Science. 1990 Nov 30;250(4985):1276-8
references: 1978759
references: J Physiol. 2005 Feb 15;563(Pt 1):249-63
references: 15611033
references: Cell. 2006 May 19;125(4):775-84
references: 16713567
references: J Neurophysiol. 2002 Nov;88(5):2664-74
references: 12424302
references: Nature. 2010 Jan 14;463(7278):232-6
references: 20075918
references: Am J Physiol Regul Integr Comp Physiol. 2002 Jun;282(6):R1710-7
references: 12010753
references: Curr Biol. 2000 Jun 29;10(13):R475-7
references: 10898970
references: Nature. 2010 Nov 11;468(7321):232-43
references: 21068832
references: N Engl J Med. 1984 Sep 27;311(13):819-23
references: 6382011
references: J Physiol. 2011 Aug 15;589(Pt 16):3929-41
references: 21690192
references: J Physiol. 2000 Feb 15;523 Pt 1:193-209
references: 10673555
references: J Comp Neurol. 1982 Apr 20;206(4):317-45
references: 7096631
references: Biochem J. 1992 Jun 1;284 ( Pt 2):491-7
references: 1318031
references: Trends Neurosci. 2007 Aug;30(8):417-24
references: 17631972
references: J Neurosci. 2009 Apr 1;29(13):3974-80
references: 19339593
references: Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R992-R1002
references: 16322352
references: Neuroscience. 2003;118(3):585-601
references: 12710969
references: Nat Neurosci. 2006 Feb;9(2):260-7
references: 16388306
references: Mol Cell Neurosci. 1993 Oct;4(5):389-97
references: 19912945
references: Commun Integr Biol. 2011 Mar;4(2):220-2
references: 21655446
references: J Neuroendocrinol. 1998 Dec;10(12):897-903
references: 9870746
references: J Neurosci. 2011 Nov 9;31(45):16064-9
references: 22072657
references: J Neuroimmunol. 1999 Oct 29;99(2):189-94
references: 10505974
references: Biochemistry. 1980 May 27;19(11):2396-404
references: 6770893
references: J Physiol. 2007 Aug 1;582(Pt 3):1219-38
references: 17525115
references: Prog Brain Res. 1998;119:101-13
references: 10074783
references: Brain Res. 1994 Aug 8;653(1-2):305-14
references: 7982066
references: J Neuroendocrinol. 2012 Feb;24(2):378-92
references: 22007724
references: Nature. 2004 Sep 9;431(7005):195-9
references: 15356633
references: Intern Med. 1998 Feb;37(2):112-22
references: 9550589
references: Science. 2005 Oct 7;310(5745):113-6
references: 16210541
references: Neuroscience. 1985 Jun;15(2):313-26
references: 3895031
references: Neuroscience. 1997 Jan;76(2):387-95
references: 9015324
references: J Neurosci. 2007 Jun 13;27(24):6473-7
references: 17567808
references: Front Neuroendocrinol. 2004 Sep-Dec;25(3-4):150-76
references: 15589267
references: Hypertension. 2002 Feb;39(2):275-80
references: 11847197
references: Endocrinology. 2006 Mar;147(3):1136-9
references: 16481483
references: Cereb Cortex. 2008 Oct;18(10):2391-401
references: 18281302
references: Neuropharmacology. 1994 Nov;33(11):1235-44
references: 7870284
references: Circ Res. 2002 Feb 8;90(2):E17-24
references: 11834719
references: Biochim Biophys Acta. 1997 Mar 20;1351(1-2):89-104
references: 9116047
references: Neuroscience. 1994 Aug;61(3):613-34
references: 7969933
references: Hippocampus. 1998;8(5):458-74
references: 9825958
references: Science. 2001 May 4;292(5518):923-6
references: 11340204
references: J Neurophysiol. 1997 Feb;77(2):527-36
references: 9065826
references: Brain Res Brain Res Rev. 1998 May;26(2-3):167-75
references: 9651518
references: J Comp Neurol. 1995 Mar 27;354(1):13-26
references: 7615871
references: Fed Proc. 1985 May;44(8):2393-9
references: 2859221
references: Nat Neurosci. 2006 Nov;9(11):1397-1403
references: 17013381
references: J Neuroendocrinol. 2012 Apr;24(4):653-63
references: 22060896
references: Nat Rev Neurosci. 2006 May;7(5):335-46
references: 16760914
references: Science. 2007 Aug 24;317(5841):1083-6
references: 17717185
references: J Physiol. 1998 Mar 1;507 ( Pt 2):463-71
references: 9518705
references: Nat Neurosci. 2005 Aug;8(8):1078-86
references: 15995701
references: Nature. 1986 Aug 21-27;322(6081):738-40
references: 3748154
references: J Biol Chem. 2000 Apr 21;275(16):11929-33
references: 10766821
references: Mol Cell Neurosci. 1992 Dec;3(6):559-70
references: 19912899
references: Philos Trans R Soc Lond B Biol Sci. 2010 Aug 12;365(1551):2375-81
references: 20603358
references: Hypertension. 2011 Sep;58(3):454-63
references: 21825233
references: Antioxid Redox Signal. 2004 Oct;6(5):878-87
references: 15345148
references: J Neurosci. 2002 Jan 1;22(1):183-92
references: 11756501
references: J Comp Neurol. 1997 Aug 25;385(2):285-96
references: 9268128
references: Nat Rev Neurosci. 2006 Feb;7(2):126-36
references: 16429122
references: J Neurosci. 2008 Nov 5;28(45):11685-94
references: 18987204
references: Circ Res. 2008 Feb 1;102(2):234-41
references: 17991880
references: J Comp Neurol. 1990 Dec 22;302(4):1019-37
references: 2081813
references: Eur J Neurosci. 1997 Dec;9(12):2532-40
references: 9517458
references: J Neuroendocrinol. 2012 Apr;24(4):566-76
references: 22128866
references: Glia. 2004 Aug 15;47(3):258-67
references: 15252815
references: J Neurosci. 2010 Dec 15;30(50):16855-63
references: 21159956
references: Kidney Int Suppl. 1997 Oct;61:S22-6
references: 9328958
references: Prog Clin Biol Res. 1990;351:349-56
references: 2236141
references: Am Heart J. 1981 Sep;102(3 Pt 2):509-14
references: 6115571
references: Nature. 1988 Mar 31;332(6163):411-5
references: 2451132
references: Endocrinology. 2006 Aug;147(8):3746-60
references: 16675519
references: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4926-31
references: 10781100
references: Biosci Rep. 2010 Jun 03;30(5):351-7
references: 20518746
references: Am J Physiol Regul Integr Comp Physiol. 2012 Aug 1;303(3):R291-300
references: 22696576
references: Auton Neurosci. 2003 Oct 31;108(1-2):17-21
references: 14614960
references: J Neurochem. 1986 Nov;47(5):1333-5
references: 3760864
references: Science. 1992 May 22;256(5060):1217-21
references: 1350383
references: J Comp Neurol. 1980 Dec 1;194(3):555-70
references: 7451682
references: Nat Neurosci. 2003 Jan;6(1):43-50
references: 12469126
references: J Physiol. 2009 Oct 1;587(Pt 19):4645-60
references: 19703969
references: Am J Physiol Heart Circ Physiol. 2001 Sep;281(3):H995-1004
references: 11514264
references: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2151-5
references: 14766975
references: Brain Res Rev. 2010 May;63(1-2):93-102
references: 19896978
references: J Physiol. 2009 Sep 1;587(Pt 17):4235-47
references: 19581379
references: Am J Physiol Regul Integr Comp Physiol. 2004 Apr;286(4):R719-25
references: 14670808
references: Neuroscience. 1997 Dec;81(4):1065-77
references: 9330368
references: Am J Physiol. 1997 Sep;273(3 Pt 2):R864-72
references: 9321861
references: J Neurosci. 1996 Oct 1;16(19):6255-64
references: 8815906
references: Brain Res. 2007 Sep 26;1171:42-51
references: 17761150
references: Neuroendocrinology. 1980 Dec;31(6):410-7
references: 6109264
references: Neurobiol Dis. 2012 Aug;47(2):268-79
references: 22542954
references: Am J Physiol. 1997 Jan;272(1 Pt 1):E126-32
references: 9038861
references: Nature. 1994 Jun 30;369(6483):744-7
references: 7911978
references: Neuroscience. 2002;113(1):221-33
references: 12123700
references: Am J Hypertens. 2000 Jun;13(6 Pt 2):112S-122S
references: 10921530
references: Trends Neurosci. 2009 Aug;32(8):421-31
references: 19615761
references: Nat Rev Immunol. 2011 Oct 25;11(11):775-87
references: 22025055
references: Brain Res. 1991 Jan 4;538(1):54-8
references: 1850319
references: Prog Neurobiol. 1991;36(2):131-69
references: 1998074
references: J Comp Neurol. 1996 Apr 15;367(4):595-606
references: 8731228
references: Nat Rev Neurosci. 2010 Feb;11(2):87-99
references: 20087359
references: Peptides. 2004 Mar;25(3):403-11
references: 15134863
references: Brain Res. 2010 Apr 22;1326:96-104
references: 20156424
references: Am J Physiol. 1997 Oct;273(4):R1474-83
references: 9362314
references: J Neurosci. 1999 May 15;19(10):4180-8
references: 10234045
references: Prog Biophys Mol Biol. 2004 Feb-Apr;84(2-3):183-96
references: 14769435
references: Pharmacol Rev. 2002 Jun;54(2):219-26
references: 12037137
references: Science. 2005 May 27;308(5726):1314-8
references: 15831717
references: Trends Neurosci. 1999 May;22(5):208-15
references: 10322493
references: Neuroscience. 1982 Apr;7(4):773-808
references: 6124897
references: J Comp Neurol. 2006 Feb 1;494(4):673-85
references: 16374796
references: Int J Cell Biol. 2012;2012:391914
references: 22719764
references: Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2264-71
references: 15148057
references: Endocrinology. 2004 Nov;145(11):5141-9
references: 15297447
references: Adv Exp Med Biol. 1999;468:175-82
references: 10635028
references: Physiol Rev. 2008 Jul;88(3):983-1008
references: 18626065
references: J Physiol. 1997 Aug 1;502 ( Pt 3):609-21
references: 9279812
references: J Neurosci Res. 2010 May 1;88(6):1364-73
references: 19938175
references: Cereb Cortex. 2003 Jun;13(6):541-9
references: 12764027
references: Neuropharmacology. 2009 Sep;57(4):343-6
references: 19577581
references: Neuroscience. 2007 Sep 7;148(3):712-23
references: 17693027
references: Neuron. 2009 Nov 12;64(3):391-403
references: 19914187
references: Nature. 1981 Apr 9;290(5806):527-8
references: 7219539
references: J Neurophysiol. 2003 Aug;90(2):786-97
references: 12904493
references: Neurochem Int. 2000 Apr;36(4-5):291-300
references: 10732996
references: J Neurosci. 1998 Mar 1;18(5):1879-85
references: 9465012
references: J Neurosci. 2002 Jun 1;22(11):4428-36
references: 12040050
references: Hypertension. 2010 Aug;56(2):297-303
references: 20547972