Abstract
Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor–receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural–glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron–glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin–angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.
Similar content being viewed by others
References
Fuxe K, Dahlstrom A, Hoistad M, Marcellino D, Jansson A, Rivera A, Diaz-Cabiale Z, Jacobsen K, Tinner-Staines B, Hagman B, Leo G, Staines W, Guidolin D, Kehr J, Genedani S, Belluardo N, Agnati LF (2007) From the Golgi-Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: wiring and volume transmission. Brain Res Rev 55(1):17–54. doi:10.1016/j.brainresrev.2007.02.009
Agnati LF, Fuxe K, Zoli M, Ozini I, Toffano G, Ferraguti F (1986) A correlation analysis of the regional distribution of central enkephalin and beta-endorphin immunoreactive terminals and of opiate receptors in adult and old male rats. Evidence for the existence of two main types of communication in the central nervous system: the volume transmission and the wiring transmission. Acta Physiol Scand 128(2):201–207. doi:10.1111/j.1748-1716.1986.tb07967.x
Fuxe K, Dahlstrom AB, Jonsson G, Marcellino D, Guescini M, Dam M, Manger P, Agnati L (2010) The discovery of central monoamine neurons gave volume transmission to the wired brain. Prog Neurobiol 90(2):82–100. doi:10.1016/j.pneurobio.2009.10.012
Fuxe K, Borroto-Escuela DO, Romero-Fernandez W, Zhang WB, Agnati LF (2013) Volume transmission and its different forms in the central nervous system. Chin J Integr Med 19(5):323–329. doi:10.1007/S11655-013-1455-1
Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21(4):575–581. doi:10.1016/j.ceb.2009.03.007
Agnati LF, Fuxe K (2014) Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks. Philos Trans R Soc Lond Ser B Biol Sci 369:1652. doi:10.1098/rstb.2013.0505
Ungerstedt U, Butcher LL, Butcher SG, Anden NE, Fuxe K (1969) Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. Brain Res 14(2):461–471
Fuxe K, Ungerstedt U (1970) Histochemical, biochemical and functional studies on central monoamine neurons after acute and chronic amphetamine administration. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York, pp 257–288
Descarries L, Watkins KC, Garcia S, Bosler O, Doucet G (1996) Dual character, asynaptic and synaptic, of the dopamine innervation in adult rat neostriatum: a quantitative autoradiographic and immunocytochemical analysis. J Comp Neurol 375(2):167–186. doi:10.1002/(SICI)1096-9861(19961111)375:2<167:AID-CNE1>3.0.CO;2-0
Bjelke B, Goldstein M, Tinner B, Andersson C, Sesack SR, Steinbusch HW, Lew JY, He X, Watson S, Tengroth B, Fuxe K (1996) Dopaminergic transmission in the rat retina: evidence for volume transmission. J Chem Neuroanat 12(1):37–50
Jansson A, Goldstein M, Tinner B, Zoli M, Meador-Woodruff JH, Lew JY, Levey AI, Watson S, Agnati LF, Fuxe K (1999) On the distribution patterns of D1, D2, tyrosine hydroxylase and dopamine transporter immunoreactivities in the ventral striatum of the rat. Neuroscience 89(2):473–489
Jansson A, Descarries L, Cornea-Hebert V, Riad M, Verge D, Bancila M, Agnati LF, Fuxe K (2002) Transmitter–receptor mismatches in central dopamine serotonin and neurpeptide systems. In: Walz W (ed) The neuronal environment: brain homeostasis in health and disease. Humana Press, Totowa, pp 83–107
Anden NE, Carlsson A, Dahlstroem A, Fuxe K, Hillarp NA, Larsson K (1964) Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci 3:523–530
Hornykiewicz O (1963) The tropical localization and content of noradrenalin and dopamine (3-hydroxytyramine) in the substantia nigra of normal persons and patients with Parkinson’s disease. Wien Klin Wochenschr 75:309–312
Thierry AM, Blanc G, Sobel A, Stinus L, Glowinski J (1973) Dopaminergic terminals in the rat cortex. Science 182(4111):499–501
Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20:140–144
Fuxe K, Lofstrom A, Hokfelt T, Ferland L, Andersson K, Agnati L, Eneroth P, Gustafsson JA, Skett P (1978) Influence of central catecholamines on LHRH-containing pathways. Clin Obstet Gynaecol 5(2):251–269
Andersson K, Fuxe K, Agnati LF, Eneroth P, Camurri M (1984) Luteinizing hormone-releasing hormone increases dopamine turnover in the lateral palisade zone of the median eminence and reduces noradrenaline turnover in the nuc. preopticus medialis of the hypophysectomized male rat. Neurosci Lett 45(3):253–258
Andersson K, Fuxe K, Eneroth P, Nyberg F, Roos P (1981) Rat prolactin and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete increases in dopamine and noradrenaline turnover in the hypophysectomized male rat. Eur J Pharmacol 76(2–3):261–265
Fuxe K, Goldstein M, Hokfelt T, Joh TH (1970) Immunohistochemical localization of dopamine–hydroxylase in the peripheral and central nervous system. Res Commun Chem Pathol Pharmacol 1(5):627–636
Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367:1–48
Fuxe K, Hamberger B, Hokfelt T (1968) Distribution of noradrenaline nerve terminals in cortical areas of the rat. Brain Res 8(1):125–131
Anden NE, Fuxe K, Larsson K (1966) Effect of large mesencephalic–diencephalic lesions on the noradrenalin, dopamine and 5-hydroxytryptamine neurons of the central nervous system. Experientia 22(12):842–843
Olson L, Fuxe K (1971) On the projections from the locus coeruleus noradrealine neurons: the cerebellar innervation. Brain Res 28(1):165–171
Nygren LG, Olson L (1977) A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord. Brain Res 132(1):85–93
Jouvet M, Pujol JF (1972) Role of monoamines in the regulation of alertness. Neurophysiological and biochemical study. Revue Neurol 127(1):115–138
Lidbrink P, Fuxe K (1973) Effects of intracerebral injections of 6-hydroxydopamine on sleep and waking in the rat. J Pharm Pharmacol 25(1):84–87
Aston-Jones G, Foote SL, Segal M (1985) Impulse conduction properties of noradrenergic locus coeruleus axons projecting to monkey cerebrocortex. Neuroscience 15(3):765–777
Olson L, Fuxe K (1972) Further mapping out of central noradrenaline neuron systems: projections of the “subcoeruleus” area. Brain Res 43(1):289–295
Del Arco A, Mora F, Mohammed AH, Fuxe K (2007) Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens. J Neural Transm 114(2):185–193. doi:10.1007/s00702-006-0533-3
Fuxe K, Borroto-Escuela DO, Romero-Fernandez W, Diaz-Cabiale Z, Rivera A, Ferraro L, Tanganelli S, Tarakanov AO, Garriga P, Narvaez JA, Ciruela F, Guescini M, Agnati LF (2012) Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks. Front Physiol 3:136. doi:10.3389/fphys.2012.00136
Fuxe K, Borroto-Escuela DO, Romero-Fernandez W, Palkovits M, Tarakanov AO, Ciruela F, Agnati LF (2014) Moonlighting proteins and protein–protein interactions as neurotherapeutic targets in the G protein-coupled receptor field. Neuropsychopharmacology 39(1):131–155. doi:10.1038/npp.2013.242
Khan ZU, Koulen P, Rubinstein M, Grandy DK, Goldman-Rakic PS (2001) An astroglia-linked dopamine D2-receptor action in prefrontal cortex. Proc Natl Acad Sci USA 98(4):1964–1969. doi:10.1073/pnas.98.4.1964
Rice ME, Cragg SJ (2008) Dopamine spillover after quantal release: rethinking dopamine transmission in the nigrostriatal pathway. Brain Res Rev 58(2):303–313. doi:10.1016/j.brainresrev.2008.02.004
Fuxe K, Jacobsen KX, Hoistad M, Tinner B, Jansson A, Staines WA, Agnati LF (2003) The dopamine D1 receptor-rich main and paracapsular intercalated nerve cell groups of the rat amygdala: relationship to the dopamine innervation. Neuroscience 119(3):733–746
Fuxe K, Rivera A, Jacobsen KX, Hoistad M, Leo G, Horvath TL, Staines W, De la Calle A, Agnati LF (2005) Dynamics of volume transmission in the brain. Focus on catecholamine and opioid peptide communication and the role of uncoupling protein 2. J Neural Transm 112(1):65–76. doi:10.1007/s00702-004-0158-3
Guidolin D, Fuxe K, Neri G, Nussdorfer GG, Agnati LF (2007) On the role of receptor–receptor interactions and volume transmission in learning and memory. Brain Res Rev 55(1):119–133. doi:10.1016/j.brainresrev.2007.02.004
Descarries L, Watkins KC, Lapierre Y (1977) Noradrenergic axon terminals in the cerebral cortex of rat. III. Topometric ultrastructural analysis. Brain Res 133(2):197–222
Strader CD, Pickel VM, Joh TH, Strohsacker MW, Shorr RG, Lefkowitz RJ, Caron MG (1983) Antibodies to the beta-adrenergic receptor: attenuation of catecholamine-sensitive adenylate cyclase and demonstration of postsynaptic receptor localization in brain. Proc Natl Acad Sci USA 80(7):1840–1844
Aoki C, Joh TH, Pickel VM (1987) Ultrastructural localization of beta-adrenergic receptor-like immunoreactivity in the cortex and neostriatum of rat brain. Brain Res 437(2):264–282
Aoki C, Rodrigues S, Kurose H (2000) Use of electron microscopy in the detection of adrenergic receptors. Methods Mol Biol 126:535–563
Aoki C, Zemcik BA, Strader CD, Pickel VM (1989) Cytoplasmic loop of beta-adrenergic receptors: synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts. Brain Res 493(2):331–347
Aoki C, Pickel VM (1992) Ultrastructural relations between beta-adrenergic receptors and catecholaminergic neurons. Brain Res Bull 29(3–4):257–263
Aoki C (1992) Beta-adrenergic receptors: astrocytic localization in the adult visual cortex and their relation to catecholamine axon terminals as revealed by electron microscopic immunocytochemistry. J Neurosci 12(3):781–792
Aoki C, Pickel VM (1992) C-terminal tail of beta-adrenergic receptors: immunocytochemical localization within astrocytes and their relation to catecholaminergic neurons in N. tractus solitarii and area postrema. Brain Res 571(1):35–49
Aoki C, Lubin M, Fenstemaker S (1994) Columnar activity regulates astrocytic beta-adrenergic receptor-like immunoreactivity in V1 of adult monkeys. Vis Neurosci 11(1):179–187
Hansson E (1990) Regional heterogeneity among astrocytes in the central nervous system. Neurochem Int 16(3):237–245
Hansson E, Ronnback L (1989) Regulation of glutamate and GABA transport by adrenoceptors in primary astroglial cell cultures. Life Sci 44(1):27–34
Hansson E, Ronnback L (1990) Astrocytes in neurotransmission: a review. Cell Mol Biol 36(5):487–496
Aoki C, Venkatesan C, Go CG, Forman R, Kurose H (1998) Cellular and subcellular sites for noradrenergic action in the monkey dorsolateral prefrontal cortex as revealed by the immunocytochemical localization of noradrenergic receptors and axons. Cereb Cortex 8(3):269–277
Milner TA, Lee A, Aicher SA, Rosin DL (1998) Hippocampal alpha2a-adrenergic receptors are located predominantly presynaptically but are also found postsynaptically and in selective astrocytes. J Comp Neurol 395(3):310–327
Itoi K, Ohara S, Kobayashi K (2013) Selective ablation of dopamine beta-hydroxylase neurons in the brain by immunotoxin-mediated neuronal targeting: new insights into brain catecholaminergic circuitry and catecholamine-related diseases. Adv Pharmacol 68:155–166. doi:10.1016/B978-0-12-411512-5.00008-7
Chandler DJ, Gao WJ, Waterhouse BD (2014) Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices. Proc Natl Acad Sci USA 111(18):6816–6821. doi:10.1073/pnas.1320827111
Chandler D, Waterhouse BD (2012) Evidence for broad versus segregated projections from cholinergic and noradrenergic nuclei to functionally and anatomically discrete subregions of prefrontal cortex. Front Behav Neurosci 6:20. doi:10.3389/fnbeh.2012.00020
Agster KL, Mejias-Aponte CA, Clark BD, Waterhouse BD (2013) Evidence for a regional specificity in the density and distribution of noradrenergic varicosities in rat cortex. J Comp Neurol 521(10):2195–2207. doi:10.1002/cne.23270
Chandler DJ, Lamperski CS, Waterhouse BD (2013) Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex. Brain Res 1522:38–58. doi:10.1016/j.brainres.2013.04.057
Robertson SD, Plummer NW, de Marchena J, Jensen P (2013) Developmental origins of central norepinephrine neuron diversity. Nat Neurosci 16(8):1016–1023. doi:10.1038/nn.3458
Agnati LF, Cortelli P, Pettersson R, Fuxe K (1995) The concept of trophic units in the central nervous system. Prog Neurobiol 46(6):561–574
Fuxe K, Marcellino D, Genedani S, Agnati L (2007) Adenosine A(2A) receptors, dopamine D(2) receptors and their interactions in Parkinson’s disease. Mov Disord 22(14):1990–2017. doi:10.1002/mds.21440
Fuxe K, Agnati LF, Benfenati F, Celani M, Zini I, Zoli M, Mutt V (1983) Evidence for the existence of receptor–receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides. J Neural Transm Suppl 18:165–179
Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M, Tinner-Staines B, Staines W, Rosin D, Terasmaa A, Popoli P, Leo G, Vergoni V, Lluis C, Ciruela F, Franco R, Ferre S (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. Neurology 61(11 Suppl 6):S19–S23
Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (2000) Direct protein–protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors. Nature 403(6767):274–280. doi:10.1038/35002014
Liu XY, Chu XP, Mao LM, Wang M, Lan HX, Li MH, Zhang GC, Parelkar NK, Fibuch EE, Haines M, Neve KA, Liu F, Xiong ZG, Wang JQ (2006) Modulation of D2R–NR2B interactions in response to cocaine. Neuron 52(5):897–909. doi:10.1016/j.neuron.2006.10.011
Lee FJ, Xue S, Pei L, Vukusic B, Chery N, Wang Y, Wang YT, Niznik HB, Yu XM, Liu F (2002) Dual regulation of NMDA receptor functions by direct protein–protein interactions with the dopamine D1 receptor. Cell 111(2):219–230
Zoli M, Agnati LF, Hedlund PB, Li XM, Ferre S, Fuxe K (1993) Receptor–receptor interactions as an integrative mechanism in nerve cells. Mol Neurobiol 7(3–4):293–334. doi:10.1007/BF02769180
Zanassi P, Paolillo M, Montecucco A, Avvedimento EV, Schinelli S (1999) Pharmacological and molecular evidence for dopamine D(1) receptor expression by striatal astrocytes in culture. J Neurosci Res 58(4):544–552
Farber K, Pannasch U, Kettenmann H (2005) Dopamine and noradrenaline control distinct functions in rodent microglial cells. Mol Cell Neurosci 29(1):128–138. doi:10.1016/j.mcn.2005.01.003
Pocock JM, Kettenmann H (2007) Neurotransmitter receptors on microglia. Trends Neurosci 30(10):527–535. doi:10.1016/j.tins.2007.07.007
Mori K, Ozaki E, Zhang B, Yang L, Yokoyama A, Takeda I, Maeda N, Sakanaka M, Tanaka J (2002) Effects of norepinephrine on rat cultured microglial cells that express alpha1, alpha2, beta1 and beta2 adrenergic receptors. Neuropharmacology 43(6):1026–1034
Tanaka KF, Kashima H, Suzuki H, Ono K, Sawada M (2002) Existence of functional beta1- and beta2-adrenergic receptors on microglia. J Neurosci Res 70(2):232–237. doi:10.1002/jnr.10399
Kettenmann H, Kirchhoff F, Verkhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77(1):10–18. doi:10.1016/j.neuron.2012.12.023
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91(22):10625–10629
Magistretti PJ, Sorg O, Naichen Y, Pellerin L, de Rham S, Martin JL (1994) Regulation of astrocyte energy metabolism by neurotransmitters. Ren Physiol Biochem 17(3–4):168–171
Magistretti PJ, Pellerin L (1996) Cellular bases of brain energy metabolism and their relevance to functional brain imaging: evidence for a prominent role of astrocytes. Cereb Cortex 6(1):50–61
Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ (1998) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20(4–5):291–299
Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443(7112):700–704. doi:10.1038/nature05193
Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O’Farrell FM, Buchan AM, Lauritzen M, Attwell D (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508(7494):55–60. doi:10.1038/nature13165
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 4 (147):147ra111. doi:10.1126/scitranslmed.3003748
Nedergaard M (2013) Neuroscience. Garbage truck of the brain. Science 340(6140):1529–1530. doi:10.1126/science.1240514
Agnati LF, Genedani S, Lenzi PL, Leo G, Mora F, Ferre S, Fuxe K (2005) Energy gradients for the homeostatic control of brain ECF composition and for VT signal migration: introduction of the tide hypothesis. J Neural Transm 112(1):45–63. doi:10.1007/s00702-004-0180-5
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M (2013) Sleep drives metabolite clearance from the adult brain. Science 342(6156):373–377. doi:10.1126/science.1241224
Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310(5745):113–116. doi:10.1126/science.1116916
Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG (2007) Synaptic islands defined by the territory of a single astrocyte. J Neurosci 27(24):6473–6477. doi:10.1523/JNEUROSCI.1419-07.2007
Hines DJ, Haydon PG (2014) Astrocytic adenosine: from synapses to psychiatric disorders. Philos Trans R Soc Lond B Biol Sci 369(1654):20130594. doi:10.1098/rstb.2013.0594
Wang N, De Bock M, Decrock E, Bol M, Gadicherla A, Vinken M, Rogiers V, Bukauskas FF, Bultynck G (1828) Leybaert L (2013) Paracrine signaling through plasma membrane hemichannels. Biochim Biophys Acta 1:35–50. doi:10.1016/j.bbamem.2012.07.002
Montero TD, Orellana JA (2015) Hemichannels: new pathways for gliotransmitter release. Neuroscience 286:45–59. doi:10.1016/j.neuroscience.2014.11.048
Gordon GR, Baimoukhametova DV, Hewitt SA, Rajapaksha WR, Fisher TE, Bains JS (2005) Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy. Nat Neurosci 8(8):1078–1086. doi:10.1038/nn1498
Porkka-Heiskanen T, Strecker RE, McCarley RW (2000) Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience 99(3):507–517
Halassa MM, Florian C, Fellin T, Munoz JR, Lee SY, Abel T, Haydon PG, Frank MG (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61(2):213–219. doi:10.1016/j.neuron.2008.11.024
Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86(3):1009–1031. doi:10.1152/physrev.00049.2005
Verkhratsky A, Burnstock G (2014) Purinergic and glutamatergic receptors on astroglia. Adv Neurobiol 11:55–79. doi:10.1007/978-3-319-08894-5_4
Lovatt D, Xu Q, Liu W, Takano T, Smith NA, Schnermann J, Tieu K, Nedergaard M (2012) Neuronal adenosine release, and not astrocytic ATP release, mediates feedback inhibition of excitatory activity. Proc Natl Acad Sci USA 109(16):6265–6270. doi:10.1073/pnas.1120997109
Wall MJ, Dale N (2013) Neuronal transporter and astrocytic ATP exocytosis underlie activity-dependent adenosine release in the hippocampus. J Physiol 591(Pt 16):3853–3871. doi:10.1113/jphysiol.2013.253450
Thrane AS, Rangroo Thrane V, Nedergaard M (2014) Drowning stars: reassessing the role of astrocytes in brain edema. Trends Neurosci 37(11):620–628. doi:10.1016/j.tins.2014.08.010
Stornetta RL, Hawelu-Johnson CL, Guyenet PG, Lynch KR (1988) Astrocytes synthesize angiotensinogen in brain. Science 242(4884):1444–1446
Milsted A, Barna BP, Ransohoff RM, Brosnihan KB, Ferrario CM (1990) Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA. Proc Natl Acad Sci USA 87(15):5720–5723
Bunnemann B, Fuxe K, Metzger R, Bjelke B, Ganten D (1992) The semi-quantitative distribution and cellular localization of angiotensinogen mRNA in the rat brain. J Chem Neuroanat 5(3):245–262
Bunnemann B, Fuxe K, Ganten D (1992) The brain renin–angiotensin system: localization and general significance. J Cardiovasc Pharmacol 19(Suppl 6):S51–S62
Aronsson M, Almasan K, Fuxe K, Cintra A, Harfstrand A, Gustafsson JA, Ganten D (1988) Evidence for the existence of angiotensinogen mRNA in magnocellular paraventricular hypothalamic neurons. Acta Physiol Scand 132(4):585–586. doi:10.1111/j.1748-1716.1988.tb08370.x
Thomas WG, Greenland KJ, Shinkel TA, Sernia C (1992) Angiotensinogen is secreted by pure rat neuronal cell cultures. Brain Res 588(2):191–200
Fuxe K, Bunnemann B, Aronsson M, Tinner B, Cintra A, von Euler G, Agnati LF, Nakanishi S, Ohkubo H, Ganten D (1988) Pre- and postsynaptic features of the central angiotensin systems. Indications for a role of angiotensin peptides in volume transmission and for interactions with central monoamine neurons. Clin Exp Hypertens Part A Theory Pract 10(Suppl 1):143–168
McCarthy CA, Widdop RE, Deliyanti D, Wilkinson-Berka JL (2013) Brain and retinal microglia in health and disease: an unrecognized target of the renin–angiotensin system. Clin Exp Pharmacol Physiol 40(8):571–579. doi:10.1111/1440-1681.12099
Unger T, Chung O, Csikos T, Culman J, Gallinat S, Gohlke P, Hohle S, Meffert S, Stoll M, Stroth U, Zhu YZ (1996) Angiotensin receptors. J Hypertens Suppl 14(5):S95–S103
Fuxe K, Agnati LF, Ganten D, Lang RE, Calza L, Poulsen K, Infantellina F (1982) Morphometric evaluation of the coexistence of renin-like and oxytocin-like immunoreactivity in nerve cells of the paraventricular hypothalamic nucleus of the rat. Neurosci Lett 33(1):19–24
Garrido-Gil P, Valenzuela R, Villar-Cheda B, Lanciego JL, Labandeira-Garcia JL (2013) Expression of angiotensinogen and receptors for angiotensin and prorenin in the monkey and human substantia nigra: an intracellular renin–angiotensin system in the nigra. Brain Struct Funct 218(2):373–388. doi:10.1007/s00429-012-0402-9
Baker KM, Chernin MI, Schreiber T, Sanghi S, Haiderzaidi S, Booz GW, Dostal DE, Kumar R (2004) Evidence of a novel intracrine mechanism in angiotensin II-induced cardiac hypertrophy. Regul Pept 120(1–3):5–13. doi:10.1016/j.regpep.2004.04.004
Erdmann B, Fuxe K, Ganten D (1996) Subcellular localization of angiotensin II immunoreactivity in the rat cerebellar cortex. Hypertension 28(5):818–824
Labandeira-Garcia JL, Garrido-Gil P, Rodriguez-Pallares J, Valenzuela R, Borrajo A, Rodriguez-Perez AI (2014) Brain renin–angiotensin system and dopaminergic cell vulnerability. Front Neuroanat 8:67. doi:10.3389/fnana.2014.00067
Hosli E, Hosli L (1986) Binding sites for [3H]dopamine and dopamine-antagonists on cultured astrocytes of rat striatum and spinal cord: an autoradiographic study. Neurosci Lett 65(2):177–182
Bal A, Bachelot T, Savasta M, Manier M, Verna JM, Benabid AL, Feuerstein C (1994) Evidence for dopamine D2 receptor mRNA expression by striatal astrocytes in culture: in situ hybridization and polymerase chain reaction studies. Brain Res Mol Brain Res 23(3):204–212
Reuss B, Unsicker K (2001) Atypical neuroleptic drugs downregulate dopamine sensitivity in rat cortical and striatal astrocytes. Mol Cell Neurosci 18(2):197–209. doi:10.1006/mcne.2001.1017
Brito V, Beyer C, Kuppers E (2004) BDNF-dependent stimulation of dopamine D5 receptor expression in developing striatal astrocytes involves PI3-kinase signaling. Glia 46(3):284–295. doi:10.1002/glia.10356
Miyazaki I, Asanuma M, Diaz-Corrales FJ, Miyoshi K, Ogawa N (2004) Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia. Brain Res 1029(1):120–123. doi:10.1016/j.brainres.2004.09.014
Vollbrecht PJ, Simmler LD, Blakely RD, Deutch AY (2014) Dopamine denervation of the prefrontal cortex increases expression of the astrocytic glutamate transporter GLT-1. J Neurochem 130(1):109–114. doi:10.1111/jnc.12697
Li A, Guo H, Luo X, Sheng J, Yang S, Yin Y, Zhou J, Zhou J (2006) Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons. FASEB J 20(8):1263–1265. doi:10.1096/fj.05-5510fje
Ohta K, Kuno S, Inoue S, Ikeda E, Fujinami A, Ohta M (2010) The effect of dopamine agonists: the expression of GDNF, NGF, and BDNF in cultured mouse astrocytes. J Neurol Sci 291(1–2):12–16. doi:10.1016/j.jns.2010.01.013
Duffy AM, Fitzgerald ML, Chan J, Robinson DC, Milner TA, Mackie K, Pickel VM (2011) Acetylcholine alpha7 nicotinic and dopamine D2 receptors are targeted to many of the same postsynaptic dendrites and astrocytes in the rodent prefrontal cortex. Synapse 65(12):1350–1367. doi:10.1002/syn.20977
Liu Y, Hu J, Wu J, Zhu C, Hui Y, Han Y, Huang Z, Ellsworth K, Fan W (2012) alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte activation. J Neuroinflamm 9:98. doi:10.1186/1742-2094-9-98
Belluardo N, Mudo G, Blum M, Fuxe K (2000) Central nicotinic receptors, neurotrophic factors and neuroprotection. Behav Brain Res 113(1–2):21–34
Di Liberto V, Mudo G, Fuxe K, Belluardo N (2014) Interactions between cholinergic and fibroblast growth factor receptors in brain trophism and plasticity. Curr Protein Pept Sci 15(7):691–702
Asanuma M, Miyazaki I, Murakami S, Diaz-Corrales FJ, Ogawa N (2014) Striatal astrocytes act as a reservoir for L-DOPA. PLoS ONE 9(9):e106362. doi:10.1371/journal.pone.0106362
Shao W, Zhang SZ, Tang M, Zhang XH, Zhou Z, Yin YQ, Zhou QB, Huang YY, Liu YJ, Wawrousek E, Chen T, Li SB, Xu M, Zhou JN, Hu G, Zhou JW (2013) Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin. Nature 494(7435):90–94. doi:10.1038/nature11748
Tanaka K, Kanno T, Yanagisawa Y, Yasutake K, Hadano S, Yoshii F, Ikeda JE (2011) Bromocriptine methylate suppresses glial inflammation and moderates disease progression in a mouse model of amyotrophic lateral sclerosis. Exp Neurol 232(1):41–52. doi:10.1016/j.expneurol.2011.08.001
Kumar U, Patel SC (2007) Immunohistochemical localization of dopamine receptor subtypes (D1R–D5R) in Alzheimer’s disease brain. Brain Res 1131(1):187–196. doi:10.1016/j.brainres.2006.10.049
Ding F, O’Donnell J, Thrane AS, Zeppenfeld D, Kang H, Xie L, Wang F, Nedergaard M (2013) alpha1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice. Cell Calcium 54(6):387–394. doi:10.1016/j.ceca.2013.09.001
Goldberg M, De Pitta M, Volman V, Berry H, Ben-Jacob E (2010) Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks. PLoS Comput Biol. doi:10.1371/journal.pcbi.1000909
Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25(21):5071–5082. doi:10.1038/sj.emboj.7601378
Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, Scemes E (2008) P2X7 receptor–Pannexin1 complex: pharmacology and signaling. Am J Physiol Cell Physiol 295(3):C752–C760. doi:10.1152/ajpcell.00228.2008
Juric DM, Loncar D, Carman-Krzan M (2008) Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors. Neurochem Int 52(1–2):297–306. doi:10.1016/j.neuint.2007.06.035
Gibbs ME, Bowser DN (2010) Astrocytic adrenoceptors and learning: alpha1-adrenoceptors. Neurochem Int 57(4):404–410. doi:10.1016/j.neuint.2010.03.020
Peng L, Li B, Du T, Kong EK, Hu X, Zhang S, Shan X, Zhang M (2010) Astrocytic transactivation by alpha2A-adrenergic and 5-HT2B serotonergic signaling. Neurochem Int 57(4):421–431. doi:10.1016/j.neuint.2010.04.018
Day JS, O’Neill E, Cawley C, Aretz NK, Kilroy D, Gibney SM, Harkin A, Connor TJ (2014) Noradrenaline acting on astrocytic beta(2)-adrenoceptors induces neurite outgrowth in primary cortical neurons. Neuropharmacology 77:234–248. doi:10.1016/j.neuropharm.2013.09.027
De Keyser J, Laureys G, Demol F, Wilczak N, Mostert J, Clinckers R (2010) Astrocytes as potential targets to suppress inflammatory demyelinating lesions in multiple sclerosis. Neurochem Int 57(4):446–450. doi:10.1016/j.neuint.2010.02.012
Laureys G, Clinckers R, Gerlo S, Spooren A, Wilczak N, Kooijman R, Smolders I, Michotte Y, De Keyser J (2010) Astrocytic beta(2)-adrenergic receptors: from physiology to pathology. Prog Neurobiol 91(3):189–199. doi:10.1016/j.pneurobio.2010.01.011
Laureys G, Gerlo S, Spooren A, Demol F, De Keyser J, Aerts JL (2014) beta(2)-adrenergic agonists modulate TNF-alpha induced astrocytic inflammatory gene expression and brain inflammatory cell populations. J Neuroinflamm 11:21. doi:10.1186/1742-2094-11-21
Hertz L, Chen Y, Gibbs ME, Zang P, Peng L (2004) Astrocytic adrenoceptors: a major drug target in neurological and psychiatric disorders? Curr Drug Targets CNS Neurol Disord 3(3):239–267
Carone C, Genedani S, Leo G, Filaferro M, Fuxe K, Agnati LF (2014) In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures. J Mol Neurosci. doi:10.1007/s12031-014-0365-9
Acknowledgments
The work was supported by the Swedish Medical Research Council (62X-00715-50-3) and by AFA Försäkring (130328) to KF and D.O.B-E. D.O.B-E belongs to Academia de Biólogos Cubanos.
Author information
Authors and Affiliations
Corresponding author
Additional information
Special Issue: In honor of Dr. Gerald Dienel.
Rights and permissions
About this article
Cite this article
Fuxe, K., Agnati, L.F., Marcoli, M. et al. Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets. Neurochem Res 40, 2600–2614 (2015). https://doi.org/10.1007/s11064-015-1574-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-015-1574-5