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Enriched environment and astrocytes in central nervous system regeneration
doi: 10.2340/16501977-0084
Abstract:
Rehabilitation medicine is entering a new era, based on the knowledge that the central nervous system has a substantial capacity for repair and regeneration. This capacity is used in 3 distinct but overlapping situations: (i) routine housekeeping throughout life (i.e. taking care of normal wear-and-tear); (ii) older age, when functional reserves of various kinds are depleted, resulting in cognitive, motor, and other deficits; and (iii) contexts in which a neurological deficit reflects an acute or chronic pathological process, such as neurotrauma, stroke, or neurodegenerative disease. The positive message here is two-fold. First, some aspects of regeneration occur even in the adult and ageing brain and spinal cord, and we are starting to unravel the underlying molecular mechanisms. Secondly, novel therapeutic approaches and targets are emerging that will substantially increase the efficiency and efficacy of rehabilitation and will transform rehabilitation into a discipline focusing both on its traditional domain and on prevention, ultimately across all the age categories. This review attempts to sum up the present knowledge about an enriched environment, currently the single most efficient plasticity- and regeneration-promoting paradigm. It also summarizes research showing that astrocytes – considered only years ago merely to nurse and support neurones – are a novel and highly interesting target for regenerative strategies in the brain and spinal cord.
Authors:
Michael Nilsson and Milos Pekny
Key words:
enriched environment, astrocytes, astrocyte intermediate filaments, plasticity, regeneration, stroke, rehabilitation, brain, stimulation.
References
- Dobkin BH. Clinical practice. Rehabilitation after stroke. N Engl J Med 2005; 352: 1677–1684.
- Gresham GE, Fitzpatrick TE, Wolf PA, McNamara PM, Kannel WB, Dawber TR. Residual disability in survivors of stroke – the Framingham study. N Engl J Med 1975; 293: 954–956.
- Richardson PM, McGuinness UM, Aguayo AJ. Axons from CNS neurons regenerate into PNS grafts. Nature 1980; 284: 264–265. Link to article
- David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 1981; 214: 931–933. Link to article
- Gimenez y Ribotta M, Menet V, Privat A. The role of astrocytes in axonal regeneration in the mammalian CNS. Prog Brain Res 2001; 132: 587–610.
- Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8: 963–970.
- Parent JM, Vexler ZS, Gong C, Derugin N, Ferriero DM. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002; 52: 802–813.
- Jin K, Sun Y, Xie L, Peel A, Mao XO, Batteur S, et al. Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 2003; 24: 171–189.
- Markham JA, Greenough WT. Experience-driven brain plasticity: beyond the synapse. Neuron Glia Biol 2004; 1: 351–363.
- Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The plastic human brain cortex. Ann Rev Neurosci 2005; 28: 377–401.
- Hummel FC, Cohen LG. Drivers of brain plasticity. Curr Opin Neurol 2005; 18: 667–674.
- Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol 2004; 61: 1844–1848.
- Hebb D. The effects of early experience on problem-solving at maturity. Am Psychol 1947; 2: 306–307.
- Will B, Galani R, Kelche C, Rosenzweig MR. Recovery from brain injury in animals: relative efficacy of environmental enrichment, physical exercise or formal training (1990–2002). Prog Neurobiol 2004; 72: 167–182.
- Rosenzweig MR, Bennett EL, Hebert M, Morimoto H. Social grouping cannot account for cerebral effects of enriched environments. Brain Res 1978; 153: 563–576. Link to article
- Mohammed AK, Jonsson G, Archer T. Selective lesioning of forebrain noradrenaline neurons at birth abolishes the improved maze learning performance induced by rearing in complex environment. Brain Res 1986; 398: 6–10. Link to article
- Whishaw IQ, Zaborowski JA, Kolb B. Postsurgical enrichment aids adult hemidecorticate rats on a spatial navigation task. Behav Neural Biol 1984; 42: 183–190. Link to article
- Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm AC. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol 2000; 164: 45–52.
- Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25: 295–301.
- Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006; 7: 697–709.
.
- Walsh RN. Effects of environmental complexity and deprivation on brain anatomy and histology: a review. Int J Neurosci 1981; 12: 33–51. Link to article
- Biernaskie J, Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci 2001; 21: 5272–5280.
- Johansson BB, Belichenko PV. Neuronal plasticity and dendritic spines: effect of environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab 2002; 22: 89–96.
- Sirevaag AM, Greenough WT. Differential rearing effects on rat visual cortex synapses. III. Neuronal and glial nuclei, boutons, dendrites, and capillaries. Brain Res 1987; 424: 320–332. Link to article
- Nilsson M, Perfilieva E, Johansson U, Orwar O, Eriksson PS. Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol 1999; 39: 569–578. Link to article
- Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 1997; 386: 493–495. Link to article
- Gobbo OL, O’Mara SM. Impact of enriched-environment housing on brain-derived neurotrophic factor and on cognitive performance after a transient global ischemia. Behav Brain Res 2004; 152: 231–241.
- Dahlqvist P, Zhao L, Johansson IM, Mattsson B, Johansson BB, Seckl JR, et al. Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats. Neurosci 1999; 93: 527–535.
- van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ. Delaying the onset of Huntington’s in mice. Nature 2000; 404: 721–722.
- Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci USA 2004; 101: 3498–3503.
- Adlard PA, Perreau VM, Pop V, Cotman CW. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci 2005; 25: 4217–4221.
- Stern Y, Gurland B, Tatemichi TK, Tang MX, Wilder D, Mayeux R. Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA 1994; 271: 1004–1010. Link to article
- Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, et al. Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci USA 2001; 98: 3440–3445.
- Mayeux R. Epidemiology of neurodegeneration. Ann Rev Neurosci 2003; 26: 81–104.
- Bezard E, Dovero S, Belin D, Duconger S, Jackson-Lewis V, Przedborski S, et al. Enriched environment confers resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic factors. J Neurosci 2003; 23: 10999–11007.
- Young D, Lawlor PA, Leone P, Dragunow M, During MJ. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med 1999; 5: 448–453. Link to article
- Biernaskie J, Chernenko G, Corbett D. Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci 2004; 24: 1245–1254.
- Dahlqvist P, Rönnback A, Bergström SA, Söderström I, Olsson T. Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats. Eur J Neurosci 2004; 19: 2288–2298.
- Hicks RR, Zhang L, Atkinson A, Stevenon M, Veneracion M, Seroogy KB. Environmental enrichment attenuates cognitive deficits, but does not alter neurotrophin gene expression in the hippocampus following lateral fluid percussion brain injury. Neurosci 2002; 112: 631–637.
- Kozlowski DA, Nahed BV, Hovda DA, Lee SM. Paradoxical effects of cortical impact injury on environmentally enriched rats. J Neurotrauma 2004; 21: 513–519.
- Passineau MJ, Green EJ, Dietrich WD. Therapeutic effects of environmental enrichment on cognitive function and tissue integrity following severe traumatic brain injury in rats. Exp Neurol 2001; 168: 373–384.
- Maegele M, Lippert-Gruener M, Ester-Bode T, Garbe J, Bouillon B, Neugebauer E, et al. Multimodal early onset stimulation combined with enriched environment is associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction after traumatic brain injury in rats. Eur J Neurosci 2005; 21: 2406–2418.
- Beaulieu CL. Rehabilitation and outcome following pediatric traumatic brain injury. The Surg Clin North Am 2002; 82: 393–408.
- Komitova M, Perfilieva E, Mattsson B, Eriksson PS, Johansson BB. Enriched environment after focal cortical ischemia enhances the generation of astroglia and NG2 positive polydendrocytes in adult rat neocortex. Exp Neurol 2006; 199: 113–121.
- Komitova M, Perfilieva E, Mattsson B, Eriksson PS, Johansson BB. Effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis and differentiation in the adult rat. J Cereb Blood Flow Metab 2002; 22: 852–860.
- Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, et al. Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci USA 2000; 97: 12880–12884.
- Sirevaag AM, Greenough WT. Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments. Brain Res 1991; 540: 273–278. Link to article
- Jones TA, Greenough WT. Ultrastructural evidence for increased contact between astrocytes and synapses in rats reared in a complex environment. Neurobiol Learn Mem 1996; 65: 48–56. Link to article
- Ullian EM, Sapperstein SK, Christopherson KS, Barres BA. Control of synapse number by glia. Science 2001; 291: 657–661.
- Halassa MM, Fellin T, Haydon PG. The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med 2007; 13: 54–63.
- Zhang Q, Haydon PG. Roles for gliotransmission in the nervous system. J Neural Transm 2005; 112: 121–125.
- Haydon PG. GLIA: listening and talking to the synapse. Nat Rev Neurosci 2001; 2: 185–193.
- Hernandez MR, Agapova OA, Yang P, Salvador-Silva M, Ricard CS, Aoi S. Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray. Glia 2002; 38: 45–64.
- Eddleston M, Mucke L. Molecular profile of reactive astrocytes–implications for their role in neurologic disease. Neurosci 1993; 54: 15–36. Link to article
- Jing R, Wilhelmsson U, Goodwill W, Li L, Pan Y, Pekny M, Skali O. Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with viemtin and GFAP intermediate filament networks. J Cell Sci 2007; 120: 1267–1277.
- Herrmann H, Hesse M, Reichenzeller M, Aebi U, Magin TM. Functional complexity of intermediate filament cytoskeletons: from structure to assembly to gene ablation. Int Rev Cytol 2003; 223: 83–175.
- Herrmann H, Aebi U. Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem 2004; 73: 749–789.
- Rueger DC, Huston JS, Dahl D, Bignami A. Formation of 100 A filaments from purified glial fibrillary acidic protein in vitro. J Mol Biol 1979; 135: 53–68. Link to article
- Renner W, Franke WW, Schmid E, Geisler N, Weber K, Mandelkow E. Reconstitution of intermediate-sized filaments from denatured monomeric vimentin. J Mol Biol 1981; 149: 285–306. Link to article
- Angelides KJ, Smith KE, Takeda M. Assembly and exchange of intermediate filament proteins of neurons: neurofilaments are dynamic structures. J Cell Biol 1989; 108: 1495–1506. Link to article
- Nakamura Y, Takeda M, Angelides KJ, Tada K, Hariguchi S, Nishimura T. Assembly, disassembly, and exchange of glial fibrillary acidic protein. Glia 1991; 4: 101–110. Link to article
- Miller RK, Vikstrom K, Goldman RD. Keratin incorporation into intermediate filament networks is a rapid process. J Cell Biol 1991; 113: 843–855. Link to article
- Wiegers W, Honer B, Traub P. Microinjection of intermediate filament proteins into living cells with and without preexisting intermediate filament network. Cell Biol Int Rep 1991; 15: 287–296. Link to article
- Vikstrom KL, Lim SS, Goldman RD, Borisy GG. Steady state dynamics of intermediate filament networks. J Cell Biol 1992; 118: 121–129. Link to article
- Yoon M, Moir RD, Prahlad V, Goldman RD. Motile properties of vimentin intermediate filament networks in living cells. J Cell Biol 1998; 143: 147–157. Link to article
- Goldman RD, Chou YH, Prahlad V, Yoon M. Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems. FASEB J 1999; 13 Suppl 2: S261–265.
- Pekny M, Eliasson C, Chien CL, Kindblom LG, Liem R,
Hamberger A, et al. GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density. Exp Cell Res 1998; 239: 332–343. Link to article
- Eliasson C, Sahlgren C, Berthold CH, Stakeberg J, Celis JE, Betsholtz C, et al. Intermediate filament protein partnership in astrocytes. J Biol Chem 1999; 274: 23996–24006.
- Pixley SK, Kobayashi Y, de Vellis J. A monoclonal antibody against vimentin: characterization. Brain Res 1984; 317: 185–199.
- Shaw G, Osborn M, Weber K. An immunofluorescence microscopical study of the neurofilament triplet proteins, vimentin and glial fibrillary acidic protein within the adult rat brain. Eur J Cell Biol 1981; 26: 68–82.
- Bushong EA, Martone ME, Jones YZ, Ellisman MH. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 2002; 22: 183–192.
- Bushong EA, Martone ME, Ellisman MH. Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development. Int J Dev Neurosci 2004; 22: 73–86.
- Wilhelmsson U, Bushong EA, Price DL, Smarr BL, Phung V, Terada M, et al. Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci USA 2006; 103: 17513–17518.
- Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature 2002; 417: 39–44.
- Morshead CM, Garcia AD, Sofroniew MV, van Der Kooy D. The ablation of glial fibrillary acidic protein-positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells. Eur J Neurosci 2003; 18: 76–84.
- Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97: 703–716.
- Imura T, Kornblum HI, Sofroniew MV. The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP. J Neurosci 2003; 23: 2824–2832.
- Laywell ED, Rakic P, Kukekov VG, Holland EC, Steindler DA. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA 2000; 97: 13883–13888.
- Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallen A, Perlmann T, et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol 1999; 145: 503–514.
- Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 1999; 2: 297–308.
- Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB,
Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24: 2143–2155.
- Menet V, Prieto M, Privat A, Gimenez y Ribotta M. Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci USA 2003; 100: 8999–9004.
- Menet V, Gimenez y Ribotta M, Chauvet N, Drian MJ, Lannoy J, Colucci-Guyon E, et al. Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression. J Neurosci 2001; 21: 6147–6158.
- Xu K, Malouf AT, Messing A, Silver J. Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. Glia 1999; 25: 390–403. Link to article
- Menet V, Gimenez YRM, Sandillon F, Privat A. GFAP null astrocytes are a favorable substrate for neuronal survival and neurite growth. Glia 2000; 31: 267–272.
- Wang X, Messing A, David S. Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein. Exp Neurol 1997; 148: 568–576. Link to article
- Cho KS, Yang L, Lu B, Feng Ma H, Huang X, Pekny M, et al. Re-establishing the regenerative potential of central nervous system axons in postnatal mice. J Cell Sci 2005; 118: 863–872.
- Nakazawa T, Takeda M, Lewis GP, Cho K-S, Jianwei J,
Wilhelmsson U, et al. Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin Invest Ophthal Vis Sci 2007 (in press).
.
- Rahpeymai Y, Hietala MA, Wilhelmsson U, Fotheringham A,
Davies I, Nilsson AK, et al. Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J 2006; 25: 1364–1374.
- Turner DA, Buhl EH, Hailer NP, Nitsch R. Morphological features of the entorhinal-hippocampal connection. Prog Neurobiol 1998; 55: 537–562. Link to article
- Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, et al. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci 2004; 24: 5016–5021.
- Lepekhin EA, Eliasson C, Berthold CH, Berezin V, Bock E, Pekny M. Intermediate filaments regulate astrocyte motility. J Neurochem 2001; 79: 617–625.
- Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, et al. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 2005; 202: 145–156.
- Goldshmit Y, Galea MP, Wise G, Bartlett PF, Turnley AM. Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J Neurosci 2004; 24: 10064–10073.
- Kinouchi R, Takeda M, Yang L, Wilhelmsson U, Lundkvist A, Pekny M, et al. Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat Neurosci 2003; 6: 863–868.
- Emsley JG, Arlotta P, Macklis JD. Star-cross’d neurons: astroglial effects on neural repair in the adult mammalian CNS. Trends Neurosci 2004; 27: 238–240.
- Pekny M, Pekna M, Wilhelmsson U, Chen DF. Response to
Quinlan and Nilsson: astroglia sitting at the controls? Trends Neurosci 2004; 27: 243–244.
- Quinlan R, Nilsson M. Reloading the retina by modifying the glial matrix. Trends Neurosci 2004; 27: 241–242.