Acetylcholine-rich neuronal grafts in the forebrain of rats: Effects of environmental enrichment, neonatal noradrenaline depletion, host transplantation site and regional source of embryonic donor cells on graft size and acetylcholinesterase-positive fibre outgrowth

The importance of several factors influencing the survival of cholinergic-rich embryonic tissue transplanted to the adult rat forebrain and the extent of acetylcholinesterase-positive fibre innervation of the host brain was investigated in 3 experiments. In the first two experiments, embryonic ventral forebrain tissue was grafted to the neocortex of rats in which the intrinsic cortical cholinergic innervation had been removed by nucleus basalis lesions. Housing the host rats in an enriched environment produced a temporary enhancement of fibre outgrowth 4 weeks after transplantation, but this was not maintained after 10 weeks. Fibre outgrowth was greater when the grafts were transplanted to the noradrenaline-depleted neocortex than to the intact neocortex. Neither environmental enrichment nor noradrenaline depletion influenced graft survival or size. In the third experiment, the embryonic donor tissue was dissected to separate regions containing precursors of the nucleus basalis cholinergic cells from regions containing precursors of the septal cholinergic cells, and transplanted to either the neocortex following nucleus basalis lesions or to the hippocampus following fimbria-fornix lesions. Nucleus basalis grafts showed greater growth in size than septal grafts, and grafts placed into the hippocampus showed greater growth in size than grafts placed into the neocortex. More interestingly, the extent of fibre outgrowth depended on the appropriateness of the donor tissue to the host transplantation site: nucleus basalis tissue showed greater acetylcholinesterase-positive outgrowth than septal tissue in the neocortex, whereas septal tissue showed greater outgrowth than nucleus basalis tissue in the hippocampus.

[1]  D. Drachman,et al.  Memory, aging and pharmacosystems , 1980 .

[2]  M. Ariel,et al.  Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Fred H. Gage,et al.  Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents , 1983, Brain Research.

[4]  A. Björklund,et al.  Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer disease. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. H. Bell,et al.  Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  A. Björklund,et al.  Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis—II. Sensorimotor and learning impairments , 1985, Neuroscience.

[7]  L. Butcher,et al.  Cholinergic and serotonergic systems in the brain and spinal cord: anatomic organization, role in intercellular communication processes, and interactive mechanisms. , 1982, Progress in brain research.

[8]  A. Björklund,et al.  Growth of transplanted monoaminergic neurones into the adult hippocampus along the perforant path , 1976, Nature.

[9]  P. Honegger,et al.  Nerve growth factor (NGF) stimulation of cholinergic telencephalic neurons in aggregating cell cultures. , 1982, Brain research.

[10]  M. Diamond.  Anatomical Brain Changes Induced by Environment , 1976 .

[11]  C. Cotman,et al.  Neurotransmitter characteristics of brain grafts: Striatal and septal tissues form the same laminated input to the hippocampus , 1983, Neuroscience.

[12]  F. Gage,et al.  Intrastriatal grafting of dopamine-containing neuronal cell suspensions: effects of mixing with target or non-target cells. , 1986, Brain research.

[13]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[14]  E. Bennett,et al.  Effects of environmental enrichment and impoverishment on rat cerebral cortex. , 1972, Journal of neurobiology.

[15]  S B Dunnett,et al.  Intracerebral grafting of neuronal cell suspensions. I. Introduction and general methods of preparation. , 1983, Acta physiologica Scandinavica. Supplementum.

[16]  N. Daw,et al.  Substantial reduction of cortical noradrenaline by lesions of adrenergic pathway does not prevent effects of monocular deprivation , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  J. Pettigrew,et al.  Restoration of visual cortical plasticity by local microperfusion of norepinephrine , 1979, The Journal of comparative neurology.

[18]  C. Cotman,et al.  Mechanisms of septal lamination in the developing hippocampus revealed by outgrowth of fibers from septal implants. I. Positional and temporal factors , 1980, Brain Research.

[19]  I. Whishaw,et al.  Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats , 1987, Neuroscience.

[20]  F. Gage,et al.  Intracerebral grafting of neuronal cell suspensions. VII. Recovery of choline acetyltransferase activity and acetylcholine synthesis in the denervated hippocampus reinnervated by septal suspension implants. , 1983, Acta physiologica Scandinavica. Supplementum.

[21]  P. Mcgeer,et al.  Choline acetyltransferase immunohistochemistry in brains of alzheimer's disease patients and controls , 1983, Neuroscience Letters.

[22]  A. Björklund,et al.  Intracephalic embryonic neural implants in the adult rat brain. I. Growth and mature organization of birainstem, cerebellar, and hippocampal implants , 1983, The Journal of comparative neurology.

[23]  A. Björklund,et al.  Functional reinnervation of the denervated neostriatum by nigral transplants , 1980, Peptides.

[24]  A. Bjo¨rklund,et al.  Transplantation of central and peripheral monoamine neurons to the adult rat brain: Techniques and conditions for survival , 1976, Brain Research.

[25]  S. Nelson,et al.  Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity , 1983, Nature.

[26]  C. Shute,et al.  The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. , 1967, Brain : a journal of neurology.

[27]  T. Maeda,et al.  Modification of postnatal development of neocortex in rat brain with experimental deprivation of locus coeruleus. , 1974, Brain research.

[28]  F. Bloom,et al.  Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat , 1975, The Journal of comparative neurology.

[29]  A. Prochiantz,et al.  Effect of striatal cells on in vitro maturation of mesencephalic dopaminergic neurones grown in serum-free conditions , 1980, Nature.

[30]  M. Blue,et al.  The effect of neonatal 6‐hydroxydopamine treatment on synaptogenesis in the visual cortex of the rat , 1982, The Journal of comparative neurology.

[31]  E. Bennett,et al.  ENRICHED ENVIRONMENTS: FACTS, FACTORS, AND FANTASIES , 1976 .

[32]  A. Bjo¨rklund,et al.  Monitoring of cell viability in suspensions of embryonic CNS tissue and its use as a criterion for intracerebral graft survival , 1985, Brain Research.

[33]  Mass action and early environment in the rat. , 1959, Journal of comparative and physiological psychology.

[34]  F. Gage,et al.  Intracerebral grafting of neuronal cell suspensions. VI. Survival and growth of intrahippocampal implants of septal cell suspensions. , 1983, Acta physiologica Scandinavica. Supplementum.

[35]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[36]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[37]  M. Molliver,et al.  The structure of cerebral cortex in the rat following prenatal administration of 6-hydroxydopamine. , 1982, Brain research.

[38]  G. Koelle,et al.  The histochemical identification of acetylcholinesterase in cholinergic, adrenergic and sensory neurons. , 1955, The Journal of pharmacology and experimental therapeutics.

[39]  A. Björklund,et al.  Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis—I. Biochemical and anatomical observations , 1985, Neuroscience.

[40]  H. Fibiger,et al.  Learning and memory deficits after lesions of the nucleus basalis magnocellularis: Reversal by physostigmine , 1985, Neuroscience.

[41]  B. Pappas,et al.  Neonatal 6-hydroxydopamine attenuates the neural and behavioral effects of enriched rearing in the rat. , 1983, European journal of pharmacology.

[42]  E. Perry,et al.  Pathological changes in the nucleus of meynert in Alzheimer's and Parkinson's diseases , 1983, Journal of the Neurological Sciences.

[43]  F. Gage,et al.  Denervation releases a neuronal survival factor in adult rat hippocampus , 1984, Nature.

[44]  T. Powell,et al.  Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer's type demonstrated by immunohistochemical staining for choline acetyltransferase , 1983, Brain Research.

[45]  D. Jacobowitz,et al.  Topographic atlas of catecholamine and acetylcholinesterase‐containing neurons in the rat brain. I. Forebrain (telencephalon, diencephalon) , 1974, The Journal of comparative neurology.

[46]  B. Lerer,et al.  Loss of cholinergic neurons in the rat neocortex produces deficits in passive avoidance learning , 1983, Pharmacology Biochemistry and Behavior.

[47]  D. Gash,et al.  Neural transplants : development and function , 1984 .

[48]  S. Bayer,et al.  Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life. , 1982, Science.

[49]  A. Björklund,et al.  Intracerebral grafting of dissociated CNS tissue suspensions: a new approach for neuronal transplantation to deep brain sites , 1981, Brain Research.

[50]  C. Sachs,et al.  Effects of 6-hydroxydopamine on central noradrenaline neurons during ontogeny , 1975, Brain Research.

[51]  M. Bear,et al.  The plastic response to monocular deprivation persists in kitten visual cortex after chronic depletion of norepinephrine , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  J. Coyle,et al.  Major innervation of newborn rat cortex by monoaminergic neurons. , 1977, Science.

[53]  F. Gage,et al.  Intracerebral grafting of neuronal cell suspensions. VIII. Survival and growth of implants of nigral and septal cell suspensions in intact brains of aged rats. , 1983, Acta physiologica Scandinavica. Supplementum.

[54]  B. Berger,et al.  In vitro maturation of mesencephalic dopaminergic neurons from mouse embryos is enhanced in presence of their striatal target cells. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[55]  A. Björklund,et al.  Septal transplants restore maze learning in rats with fornix-fimbria lesions , 1982, Brain Research.

[56]  S. Hunt,et al.  The substantia innominata in alzheimer's disease: an histochemical and biochemical study of cholinergic marker enzymes , 1982, Neuroscience Letters.

[57]  C. Cotman,et al.  Neuronotrophic activity in brain wounds of the developing rat. Correlation with implant survival in the wound cavity , 1983, Brain Research.

[58]  D L Price,et al.  Alzheimer's disease: a disorder of cortical cholinergic innervation. , 1983, Science.

[59]  A. Bjo¨rklund,et al.  In vivo evidence for a hippocampal adrenergic neuronotrophic factor specifically released on septal deafferentation , 1981, Brain Research.

[60]  C. Shute,et al.  The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. , 1967, Brain : a journal of neurology.

[61]  F. Bloom,et al.  Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. I. Cell differentiation , 1974, The Journal of comparative neurology.

[62]  L. Olson,et al.  Trophic effects of brain areas on the developing cerebral cortex: I. Growth and histological organization of intraocular grafts. , 1983, Brain research.

[63]  D. Felten,et al.  Evidence for a neurotrophic role of noradrenaline neurons in the postnatal development of rat cerebral cortex , 1982 .

[64]  C. Cotman,et al.  The survival of brain transplants is enhanced by extracts from injured brain. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[65]  M R Rosenzweig,et al.  Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats. , 1977, Journal of comparative and physiological psychology.

[66]  R. Sutherland,et al.  Cortical noradrenaline depletion eliminates sparing of spatial learning after neonatal frontal cortex damage in the rat , 1982, Neuroscience Letters.

[67]  M. Schwab,et al.  Nerve growth factor increases choline acetyl-transferase but not survival or fiber outgrowth of cultured fetal septal cholinergic neurons , 1985, Neuroscience.

[68]  I. Whishaw,et al.  Postsurgical enrichment aids adult hemidecorticate rats on a spatial navigation task. , 1984, Behavioral and neural biology.

[69]  G. D. Das.  Neural Transplantation in Mammalian Brain: Some Conceptual and Technical Considerations , 1983 .

[70]  B. Will,et al.  Effets de l'environnement sur la restauration fonctionnelle après lésions hippocampiques chez des rats adultes , 1978, Physiology & Behavior.

[71]  R. Laverty,et al.  Long‐lasting peripheral and central effects of 6‐hydroxydopamine in rats , 1972, British journal of pharmacology.

[72]  J. Pettigrew,et al.  Preservation of binocularity after monocular deprivation in the striate cortex of kittens treated with 6‐Hydroxydopamine , 1979, The Journal of comparative neurology.

[73]  D. Amaral,et al.  The effects of neonatal 6‐hydroxydopamine treatment on morphological plasticity in the dentate gyrus of the rat following entorhinal lesions , 1980, The Journal of comparative neurology.

[74]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[75]  P. Levitt,et al.  Development of the noradrenergic innervation of neocortex , 1979, Brain Research.

[76]  S. Iversen,et al.  Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats , 1984, Behavioural Brain Research.

[77]  F. Hefti,et al.  Chronic intraventricular injections of nerve growth factor elevate hippocampal choline acetyltransferase activity in adult rats with partial septo-hippocampal lesions , 1984, Brain Research.

[78]  D M Bowen,et al.  Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. , 1976, Brain : a journal of neurology.

[79]  C. Cotman,et al.  Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. , 1982, Science.

[80]  S. Dunnett,et al.  Acetylcholine-rich transplants in the hippocampus: influence of intrinsic growth factors and application of nerve growth factor on choline acetyltransferase activity , 1985, Brain Research.

[81]  G. Pepeu,et al.  Lesions of cholinergic forebrain nuclei: Changes in avoidance behavior and scopolamine actions , 1982, Pharmacology Biochemistry and Behavior.

[82]  Robert H. Perry,et al.  Neurotransmitter enzyme abnormalities in senile dementia Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue , 1977, Journal of the Neurological Sciences.

[83]  I. Whishaw,et al.  Disruption of central cholinergic systems in the rat by basal forebrain lesions or atropine: Effects on feeding, sensorimotor behaviour, locomotor activity and spatial navigation , 1985, Behavioural Brain Research.

[84]  M. Blue,et al.  The role of the noradrenergic system on the formation of synapses in the visual cortex of the rat. , 1982, Brain research.

[85]  R. Bartus,et al.  Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat , 1983, Pharmacology Biochemistry and Behavior.

[86]  S. Finger,et al.  Brain Damage and Recovery: Research and Clinical Perspectives , 1983 .

[87]  C. Cotman,et al.  Injury-induced neuronotrophic activity in adult rat brain: correlation with survival of delayed implants in the wound cavity , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.