Abstract
Cerebral cortex contains few if any galanin neurons, but receives galaninergic inputs from subcortical areas. Apart from our earlier study on the response to cortical spreading depression, little is known about the presence and function of galanin in normal or injured cortex and to gain more insight into its possible roles, we investigated the temporal effects of focal ischemia on the expression of galanin and galanin receptors (GalRs). Focal ischemia induced in the rat by unilateral middle cerebral artery occlusion increased galanin and GalR1 mRNAs in penumbral/undamaged areas on the first and second day post-ischemia, while increased GalR2 mRNA was observed in the same regions only on the second day. Immunohistochemical studies revealed galanin immunoreactive neurons in the frontal/cingulate cortex and abundant galanin-immunoreactivity in nerve axons/fibres within the penumbral areas, between the third and the seventh day after ischemia. Galanin mRNA and immunoreactivity was also increased in a population of small cells thought to be NG2-positive oligodendrocyte precursors. Up-regulation of galanin and GalRs in various cell populations following severe ischemic injury further demonstrates the marked plasticity of galanin and GalR1/2 expression after brain injury, and together with data reported elsewhere in this volume, suggests a functional role for galanin signalling in such pathophysiological conditions.
Keywords
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- 1.
An account of these findings appeared in abstract form – Shen P-J, Gundlach AL (2001) Complex responses of cortical galanin systems to spreading depression and focal ischemia. J Neurochem 78(Suppl 1):165.
Abbreviations
- GalR:
-
Galanin receptor
- MCAo:
-
Middle cerebral artery occlusion
- RMS:
-
Rostral migratory stream
- SVZ:
-
Subventricular zone
References
Tatemoto K, Rökaeus Å, Jörwall H, McDonald TJ, Mutt V (1983) Galanin – a novel biologically active peptide from porcine intestine. FEBS Lett 164:124–128
Hökfelt T, Bartfai T, Crawley J (1998) Galanin: Basic research discoveries and therapeutic implications. The New York Academy of Sciences, New York
Melander T, Hökfelt T, Rökaeus Å (1986) Distribution of galanin like immunoreactivity in the rat central nervous system. J Comp Neurol 248:475–517
Merchenthaler I, López FJ, Negro-Vilar A (1993) Anatomy and physiology of central galanin-containing pathways. Prog Neurobiol 40:711–769
Ryan MC, Gundlach AL (1996) Localization of preprogalanin messenger RNA in rat brain: identification of transcripts in a subpopulation of cerebellar Purkinje cells. Neuroscience 70:709–728
Habert-Ortoli E, Amiranoff B, Loquet I, Laburthe M, Mayaux JF (1994) Molecular cloning of a functional human galanin receptor. Proc Natl Acad Sci USA 91:9780–9783
Howard AD, Tan C, Shiao L-L, Palyha OC, McKee KK, Weinberg DH, Feighner SD, Cascieri MA, Smith RG, Van Der Ploeg LHT, Sullivan KA (1997) Molecular cloning and characterization of a new receptor for galanin. FEBS Lett 405:285–290
Wang S, Hashemi T, He C, Strader C, Bayne M (1997) Molecular cloning and pharmacological characterization of a new galanin receptor subtype. Mol Pharmacol 52:337–343
Branchek TA, Smith KE, Gerald C, Walker MW (2000) Galanin receptor subtypes. Trends Pharmacol Sci 21:109–116
Gundlach AL (2002) Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol 440:255–268
Kinney JW, Starosta G, Crawley JN (2003) Central galanin administration blocks consolidation of spatial learning. Neurobiol Learn Mem 80:42–54
Liu HX, Brumovsky P, Schmidt R, Brown W, Payza K, Hodzic L, Pou C, Godbout C, Hökfelt T (2001) Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: Selective actions via GalR1 and GalR2 receptors. Proc Natl Acad Sci USA 98:9960–9964
Melander T, Hökfelt T, Rökaeus Å, Cuello AC, Oertel WH, Verhofstad A, Goldstein M (1986) Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J Neurosci 6:3640–3654
Kinney GA, Emmerson PJ, Miller RJ (1998) Galanin receptor-mediated inhibition of glutamate release in the arcuate nucleus of the hypothalamus. J Neurosci 18:3489–3500
Pieribone VA, Xu Z-QD, Zhang X, Hökfelt T (1998) Electrophysiologic effects of galanin on neurons of the central nervous system. In: Hökfelt T, Bartfai T, Crawley J (eds) Galanin: Basic research discoveries and therapeutic implications. The New York Academy of Sciences, New York, pp 264–273
Xu Z-QD, Ma X, Soomets U, Langel U, Hökfelt T (1999) Electrophysiological evidence for a hyperpolarizing galanin (1-15)-selective receptor on hippocampal CA3 pyramidal neurons. Proc Natl Acad Sci USA 96:14583–14587
Hökfelt T, Broberger C, Xu Z-QD, Sergeyev V, Ubink R, Diez M (2000) Neuropeptides – an overview. Neuropharmacology 39:1337–1356
Anisimov SV, Tarasov KV, Tweedie D, Stern MD, Wobus AM, Boheler KR (2002) SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells. Genomics 79:169–176
Berger A, Tuechler C, Almer D, Kogner P, Ratschek M, Kerbl R, Iismaa TP, Jones N, Sperl W, Kofler B (2002) Elevated expression of galanin receptors in childhood neuroblastic tumors. Neuroendocrinology 75:130–138
Perel Y, Amrein L, Dobremez E, Rivel J, Daniel JY, Landry M (2002) Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status. Br J Cancer 86:117–122
Shen P-J, Larm JA, Gundlach AL (2003) Expression and plasticity of galanin systems in cortical neurons, oligodendrocyte progenitors and proliferative zones of normal brain and after spreading depression. Eur J Neurosci 18:1362–1376
Shen P-J, Yuan C-G, Ma J, Cheng S, Yao M, Turnley AM, Gundlach AL (2005) Galanin in neuro(glio)genesis: expression of galanin and receptors by progenitor cells in vivo and in vitro and effects of galanin on neurosphere proliferation. Neuropeptides 39:201–205
Xia CY, Yuan CX, Yuan CG (2005) Galanin inhibits the proliferation of glial olfactory ensheathing cells. Neuropeptides 39:453–459
Tofighi R, Joseph B, Xia S, Xu ZQ, Hamberger B, Hökfelt T, Ceccatelli S (2008) Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2). Proc Natl Acad Sci USA 105:2717–2722
Mazarati A, Lu X, Shinmei S, Badie-Mahdavi H, Bartfai T (2004) Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GalR1) knockout mice. Neuroscience 128:431–441
Jungnickel SR-F, Yao M, Shen P-J, Gundlach AL (2005) Induction of galanin receptor-1 (GalR1) expression in external granule cell layer of postnatal mouse cerebellum. J Neurochem 92:1452–1462
Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092–1094
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317
Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95:3168–3171
Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148
Betarbet R, Zigova T, Bakay RA, Luskin MB (1996) Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone. Int J Dev Neurosci 14:921–930
Weinstein DE, Burrola P, Kilpatrick TJ (1996) Increased proliferation of precursor cells in the adult rat brain after targeted lesioning. Brain Res 743:11–16
Parent JM (2007) Adult neurogenesis in the intact and epileptic dentate gyrus. Prog Brain Res 163:529–540
Zhang RL, Zhang ZG, Zhang L, Chopp M (2001) Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia. Neuroscience 105:33–41
Tanaka K, Nogawa S, Ito D, Suzuki S, Dembo T, Kosakai A, Fukuuchi Y (2001) Activation of NG2-positive oligodendrocyte progenitor cells during post-ischemic reperfusion in the rat brain. NeuroReport 12:2169–2174
Zea Longa E, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91
Burazin TCD, Larm JA, Ryan MC, Gundlach AL (2000) Galanin-R1 and -R2 receptor mRNA expression during the development of rat brain suggests differential subtype involvement in synaptic transmission and plasticity. Eur J Neurosci 12:2901–2917
Theodorsson A, Theodorsson E (2005) Estradiol increases brain lesions in the cortex and lateral striatum after transient occlusion of the middle cerebral artery in rats: no effect of ischemia on galanin in the stroke area but decreased levels in the hippocampus. Peptides 26:2257–2264
De Michele M, Sancesario G, Toni D, Ciuffoli A, Bernardi G, Sette G (2006) Specific expression of galanin in the peri-infarct zone after permanent focal cerebral ischemia in the rat. Regul Pept 134:38–45
O’Donnell D, Ahmad S, Wahlestedt C, Walker P (1999) Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. J Comp Neurol 409:469–481
Melander T, Köhler C, Nilsson S, Hökfelt T, Brodin E, Theodorsson E, Bartfai T (1988) Autoradiographic quantitation and anatomical mapping of 125I-galanin binding sites in the rat central nervous system. J Chem Neuroanat 1:213–233
Raghavendra Rao VL, Bowen KK, Dhodda VK, Song G, Franklin JL, Gavva NR, Dempsey RJ (2002) Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia. J Neurochem 83:1072–1086
Raghavendra Rao VL, Dhodda VK, Song G, Bowen KK, Dempsey RJ (2003) Traumatic brain injury-induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis. J Neurosci Res 71:208–219
Cheung RT, Cechetto DF (2000) Neuropeptide Y-Y1 receptor antisense oligodeoxynucleotide increases the infarct volume after middle cerebral artery occlusion in rats. Neuroscience 98:771–777
Chen SH, Cheung RT (2003) Intracerebroventricular injection of a neuropeptide Y-Y1 receptor agonist increases while BIBP3226, a Y1 antagonist, reduces the infarct volume following transient middle cerebral artery occlusion in rats. Neuroscience 116:119–126
Aakerlund L, Gether U, Fuhlendorff J, Schwartz TW, Thastrup O (1990) Y1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase. FEBS Lett 260:73–78
Smiałowska M, Domin H, Zieba B, Koźniewska E, Michalik R, Piotrowski P, Kajta M (2009) Neuroprotective effects of neuropeptide Y-Y2 and Y5 receptor agonists in vitro and in vivo. Neuropeptides 43:235–249
Zachariou V, Georgescu D, Kansal L, Merriam P, Picciotto MR (2001) Galanin receptor 1 gene expression is regulated by cyclic AMP through a CREB-dependent mechanism. J Neurochem 76:191–200
Badie-Mahdavi H, Lu X, Behrens MM, Bartfai T (2005) Role of galanin receptor 1 and galanin receptor 2 activation in synaptic plasticity associated with 3', 5'-cyclic AMP response element-binding protein phosphorylation in the dentate gyrus: studies with a galanin receptor 2 agonist and galanin receptor 1 knockout mice. Neuroscience 133:591–604
Burazin TCD, Gundlach AL (1998) Inducible galanin and GalR2 receptor system in motor neuron injury and regeneration. J Neurochem 71:879–882
Elliott-Hunt CR, Pope RJ, Vanderplank P, Wynick D (2007) Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage. J Neurochem 100:780–789
Wraith DC, Pope RJ, Butzkueven H, Holder H, Vanderplank P, Lowrey P, Day MJ, Gundlach AL, Kilpatrick TJ, Scolding N, Wynick D (2009) A role for galanin in human and experimental inflammatory demyelination. Proc Natl Acad Sci USA 106:15466–15471
Levine JM, Reynolds R, Fawcett JW (2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci 24:39–47
Dawson MR, Levine JM, Reynolds R (2000) NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J Neurosci Res 61:471–479
Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22
Acknowledgments
This research was supported by research grants from the National Health and Medical Research Council of Australia and the Austin Hospital Medical Research Foundation.
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Shen, PJ., Gundlach, A.L. (2010). Galanin Systems and Ischemia: Peptide and Receptor Plasticity in Neurons and Oligodendroglial Precursors. In: Hökfelt, T. (eds) Galanin. Experientia Supplementum, vol 102. Springer, Basel. https://doi.org/10.1007/978-3-0346-0228-0_15
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DOI: https://doi.org/10.1007/978-3-0346-0228-0_15
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