Cellular delivery of human CNTF prevents motor and cognitive dysfunction in a rodent model of Huntington's disease

Cell Transplantation

Volumn 6, Issue 3, 1997, Pages 249-266

  Emerich, Dwaine F ^a,b   Cain, Chris K ^a   Greco, Corinne ^a   Saydoff, Joel A ^a   Hu, Zhong Yi ^a   Liu, Hanjiu ^a   Lindner, Mark D ^a  

^a CytoTherapeutics Inc   (United States)

^b ALKERMES INC   (United States)

Author keywords

CNTF; Fibroblast; Huntington's disease; Polymer; Quinolinic acid; Striatum

Indexed keywords

CHOLINE ACETYLTRANSFERASE; CILIARY NEUROTROPHIC FACTOR; GLUTAMATE DECARBOXYLASE; QUINOLINIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL STRAIN BHK; CELL TRANSPLANTATION; COGNITIVE DEFECT; CONTROLLED STUDY; EXPRESSION VECTOR; HUNTINGTON CHOREA; HYPERACTIVITY; LATENT PERIOD; LATERAL BRAIN VENTRICLE; MALE; MAZE TEST; MORTALITY; MOTOR PERFORMANCE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT; WEIGHT REDUCTION; WORKING MEMORY;

ANIMALS; BEHAVIOR, ANIMAL; BODY WEIGHT; CAPSULES; CELLS, CULTURED; CHOLINE O-ACETYLTRANSFERASE; CILIARY NEUROTROPHIC FACTOR; COGNITION DISORDERS; CORPUS STRIATUM; CRICETINAE; DENERVATION; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FIBROBLASTS; GENE EXPRESSION; GLUTAMATE DECARBOXYLASE; HAND STRENGTH; HUMANS; HUNTINGTON DISEASE; KIDNEY; MALE; MAZE LEARNING; MOTOR ACTIVITY; NERVE GROWTH FACTORS; NERVE TISSUE PROTEINS; QUINOLINIC ACID; RATS; RATS, SPRAGUE-DAWLEY; SURVIVAL ANALYSIS; TOUCH; TRANSFECTION;

ANIMALIA; CRICETINAE; RODENTIA;

EID: 0030911441     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0963-6897(97)00035-3     Document Type: Article

References (104)

1. Abrous, D.N.; Dunnett, S.B. Paw Reaching in rats - The staircase test. In: Wouterlood, F.G.; ed. Neuroscience Protocols, Module 3. New York: Elsevier Science Pub.; 1994:19-29.
2. Aebischer, P.; Schluep, M.; Deglon, N.; Joseph, J.M.; Hirt, L.; Heyd, B.; Goddard, M.; Hammang, J.P.; Zürn, A.D.; Kato, A.C.; Regli, F.; Baetge, E.E. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat. Med 2:696-699; 1996.
3. Albers, R.W.; Brady, R.O. The distribution of glutamic acid decarboxylase in the nervous system of the rhesus monkey. J. Biol. Chem. 234:926-928; 1959.
4. Albin, R.L.; Greenamyre, J.T. Alternative excitotoxic hypothesis. Neurology 42:733-738; 1992.
5. Anderson, K.D.; Panayotatos, N.; Cordoran, T.L.; Lindsay, R.M.; Wiegand, S.J. Ciliary neurotrophic factor protects striatal output neurons in an animal model of Huntington's disease. Proc. Natl. Acad. Sci. USA 93: 7346-7351; 1996.
6. Apfel, S.C.; Arezzo, J.C.; Moran, M.; Kessler; J.A. Effects of administration of ciliary neurotrophic factor on normal motor and sensory peripheral nerves in vivo. Brain Res. 604:1-6; 1993.
7. Arakawa, Y.; Sendtner, M.; Thoenen, H. Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: Comparison with other neurotrophic factors and cytokines. J. Neurosci. 10:3507-3515; 1990.
8. Baetge, E.E.; Suh, Y.H.; Joh, T.H. Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial homology with rat tyrosine hydroxylase. Proc. Natl. Acad. Sci. USA 83: 5454-5458; 1986.
9. Beal, M.F.; Kowall, N.W.; Ellison, D.W.; Mazurek, M.F.; Swartz, K.J.; Martin, J.B. Replication of the neurochemical characteristics Huntington's disease by quinolinic acid. Nature 321:168-171; 1986.
10. Beal, M.F.; Mazurek, M.F.; Ellison, D.W.; Swartz, K.J.; McGarvey, U.; Bird, E.D.; Martin, J.B. Somatostatin and neuropeptide Y concentrations in pathologically graded cases of Huntington's disease. Ann. Neurol. 23:562-569; 1988.
11. Beal, M.F.; Kowall, N.W.; Swartz, K.J.; Ferranti, R.J.; Martin, J.B. Differential sparing of somatostatinneuropeptide Y and cholinergic neurons following striatal excitotoxin lesions. Synapse 3:38-47 1989.
12. Beal, M.F. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?. Ann. Neurol. 31:119-130; 1992.
13. Bird, E.D. Chemical pathology of Huntington's disease. Annu. Rev. Pharmacol. Toxicol. 20:533-551; 1980.
14. Block, F.; Kunkel, M.; Schwarz, M. Quinolinic acid lesion of the striatum induces impairment in spatial learning and motor performance in rats. Neurosci. Lett. 149:126-128; 1993.
15. Breakefield, X.O. Combining CNS transplantation and gene transfer. Neurobiol. Aging 10:647-648; 1989.
16. Buck, S.H.; Burks, T.F.; Brown, M.R.; Yamamura, H.I. Reduction in basal ganglia and substantia nigra substance P levels in Huntington's disease. Brain Res. 209:464-469; 1981.
17. Buisson, A.; Pateau, V.; Plotkine, M.; Boulu, R.G. Nigrostriatal pathway modulates striatum vulnerability to quinolinic acid. Neurosci. Lett. 131:257-259; 1991.
18. Burns, A.; Psych, M.R.C.; Folstein, S.; Brandt, J.; Folstein, M. Clinical assessment of irritability, aggression, and apathy in Huntington and Alzheimer disease. J. Nervous Mental Dis 178:20-26; 1990.
19. Cabasso, I. Hollow fiber membranes. In: Kirk-Othmer, ed. Encyclopedia of chemical technology, vol. 12. New York:Wiley; 1981:492-517.
20. Choi, D.W. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623-634; 1988.
21. Clatterbuck, R.E.; Price, D.L.; Koliatsos, V.E. Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system. Proc. Natl. Acad. Sci. USA 90:2222-2226; 1993.
22. Cummings, J.L.; Benson, D.F. Psychological dysfunction accompanying subcortical dementias. Annu. Rev. Med. 39:53-61; 1988.
23. Dewhurst, K.; Oliver, J.; Trick, K.L.K.; McKnight, A.L. Neuropsychiatric aspects of Huntington's disease. Confinia Neurol. 31:258-268; 1979.
24. DiFiglia, M. Excitotoxic injury of the neostriatum: A model for Huntington's disease. Trends Neurosci. 13: 286-289; 1990.
25. Dodd, D.H.; Schultz, R.F., Jr. Computational procedures for estimating magnitude of effect for some analysis of variance designs. Psychol. Bull. 79:391-395; 1973.
26. Dunnett, S.B. Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats. Psychopharmacology (Berlin) 87: 357-363; 1985.
27. Dunnett, S.B.; Evenden, J.L.; Iversen, S.D. Delay-dependent short-term memory deficits in aged rats. Psychopharmacology (Berlin) 96:174-180; 1988.
28. Emerich, D.F.; Zubricki, E.M.; Shipley, M.T.; Norman, A.B.; Sanberg, P.R. Female rats are more sensitive to the locomotor alterations following quinolinic acid-induced striatal lesions: Effects of striatal transplants. Exp. Neurol. 111:369-378; 1991.
29. Emerich, D.F.; Sanberg, P.R. Animal models in Huntington's disease. In: Boulton, A.A.; Baker, G.B.; Butterworth, R.F., eds. Neuromethods, vol. 17, Animal models of neurological disease, vol. 17. Clifton, NJ: Humana Press; 1992:65-134.
30. Emerich, D.F.; Sanberg, P.R. Animal models in Huntington's disease. In: Boulton, A.A.; Baker, G.B.; Butterworth, R.F., eds. Neuromethods, vol. 17, Animal models of neurological disease, vol. 17. Clifton, NJ: Humana Press; 1992:65-134.
31. Emerich, D.F.; Frydel, B.; McDermott, P.; Krueger, P.; Lavoie, M.; Sanberg, P.R.; Winn, S.R. Polymerencapsulated PC 12 cells promote recovery of motor function in aged rats. Exp. Neurol. 122:37-47; 1993.
32. Emerich, D.F.; Winn, S.R.; Harper, J.; Hammang, J.P.; Baetge, E.E.; Kordower, J.H. Transplantation of polymerencapsulated cells genetically modified to secrete human nerve growth factor prevents the loss of degenerating cholinergic neurons in nonhuman primates. J. Comp. Neurol. 349:148-164; 1994.
33. Emerich, D.F.; Hammang, J.P.; Baetge, E.E.; Winn, S.R. Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behav-ioral and neuropathological consequences of quinolinic acid injections into rodent striatum. Exp. Neurol. 130: 141-150; 1994.
34. Emerich, D.F.; Lindner, M.D.; Winn, S.R.; Chen, E.-Y.; Frydel, B.R.; Kordower, J.H. Implants of encapsulated human CNTF-producing fibroblasts prevent behavioral deficits and striatal degeneration in a rodent model of Huntington's disease. J. Neurosci. 16:5168-5181; 1996.
35. Ferrante, R.J.; Beal, M.F.; Kowall, N.W.; Richardson, E.P.; Martin J.B. Sparing of acetylcholinesterase-containing striatal neurons in Huntington's disease. Brain Res. 415:178-182; 1987.
36. Folstein, S.E.; Franz, M.L.; Jensen, B.A.; Chase, G.A.; Folstein, M.F. Conduct disorder and affective disorder among the offspring of patients with Huntington's disease. Psychol. Med. 13:537-542; 1983.
37. Fonnum, F. Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem. J. 115:465-472; 1969.
38. Forger, N.G.; Roberts, S.L.; Wong, V.; Breedlove, S.M. Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats. J. Neurosci. 13: 4720-4726; 1993.
39. Frim, D.M.; Schumacher, J.M.; Short, M.P.; Breakefield, X.O.; Isacson, O. Local response to intracerebral grafts of NGF-secreting fibroblasts: Induction of a peroxidative enzyme. Soc. Neurosci. Abstr. 18:1100; 1992.
40. Frim, D.M.; Uhler, T.A.; Short, M.P.; Exxedine, Z.D.; Klagsbrun, M.; Breakefield, X.O.; Isacson, O. Effects of biologically delivered NGF, BDNF, and bFGF on striatal excitotoxic lesions. Neuroreport 4:367-370; 1993.
41. Frim, D.M.; Simpson, J.; Uhler, T.A.; Short, M.P.; Bossi, S.R.; Breakefield, X.O.; Isacson, O. Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF. J. Neurosci. Res. 35:452-458; 1993.
42. Furtado, J.C.S.; Mazurek, M.F. Behavioral characterization of quinolinate-induced lesions of the medial striatum: Relevance for Huntington's disease. Exp. Neurol. 138: 158-168; 1996.
43. Gage, F.H.; Wolf, J.A.; Rosenberg, M.B.; Xu, L.; Yee, J.K. Grafting genetically modified cells to the brain: Possibilities for the future. Neuroscience 23:795-807; 1987.
44. Hagg, T.; Quon, D.; Higaki, J.; Varon, S. Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS. Neuron 8:145-158; 1993.
45. Hagg, T.; Varon, S. Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo. Proc. Natl. Acad. Sci. USA 90:6315-6319; 1993.
46. Hantraye, P.; Riche, D.; Maziere, M.; Isacson, O. A primate model of Huntington's disease: Behavioral and anatomical studies of unilateral excitotoxic lesions of the caudate-putamen in the baboon. Exp. Neurol. 108:91-104; 1990.
47. Hoyle, G.W.; Mercer, E.H.; Palmiter, R.D.; Brinster, R.L. Expression of NGF in sympathetic neurons leads to excessive axon outgrowth from ganglia but decreased terminal innervation within tissues. Neuron 10:1019-1034; 1993.
48. Isacson, O.; Riche, D.; Hantraye, P.; Sofroniew, M.V.; Maziere, M. A primate model of Huntington's disease; Cross-species implantation of striatal precursor cells to the excitotoxically lesioned baboon caudate-putamen. Exp. Brain Res. 75:213-220; 1989.
49. Isacson, O.; Hantraye, P.; Maziere, M.; Sofroniew, M.V.; Riche, D. Apomorphine-induced dyskinesias after excitotoxic caudate-putamen lesions and the effects of neural transplantation in non-human primates. Prog. Brain Res. 82:523-533; 1990.
50. Jackson, G.; Apffel, L.; Werrbach-Perez, K.; Perez-Polo, J.R. Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. I. Stimulation of hydrogen peroxide resistance. J. Neurosci. Res. 25:360-368; 1990.
51. Kawaja, M.D.; Fagan, A.M.; Firestein, B.L.; Gage, F.H. Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure. J. Comp. Neurol. 307:695-706; 1991.
52. Kawaja, M.D.; Rosenberg, M.B.; Yoshida, K.; Gage, F.H. Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats. J. Neurosci. 12:2849-2864; 1992.
53. Kirk, R.E. Experimental design: Procedures for the behavioral sciences. Pacific Grove, CA: Brooks/Cole Publishing Company; 1982.
54. Kordower, J.H.; Winn, S.R.; Liu, Y.-T.; Mufson, E.J.; Sladek, J.R., Jr.; Baetge, E.E.; Hammang, J.P.; Emerich, D.F. The aged monkey basal forebrain: Rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor. Proc. Natl. Acad. Sci. USA 91:10898-10902; 1994.
55. Kordower, J.H.; Charles, V.; Bayer, R.; Bartus, R.; Putney, S.; Walus, L.R.; Friden, P.M. Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington's disease. Proc. Natl. Acad. Sci. USA 91:9077-9080; 1994.
56. Kordower, J.H.; Chen, E.-Y.; Mufson, E.J.; Winn, S.R.; Emerich, D.F. Intrastriatal implants of polymerencapsulated cells genetically modified to secrete human NGF trophic effects upon cholinergic and noncholinergic neurons. Neuroscience 72:63-77; 1996.
57. Kumon, Y.; Sakaki, S.; Watanabe, H.; Nakano, K.; Ohta, S.; Matsuda, S.; Yoshimura, H.; Sakanaka, M. Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia. Neurosci. Lett. 206:141-144; 1996.
58. Neurotoxicity risk assessment. In: Neurobehavioral toxicity: Analysis and interpretation. Weiss, B., Odonoghue J.L., eds., New York: Raven Press; 1994:253-262.
59. Legay, F.; Pelhate, S.; Tappaz, M.L. Phylogenesis of brain glutamic acid decarboxylase from vertebrates: Immunochemical studies. J. Neurochem. 46:1478-1486; 1986.
60. Levivier, M.; Przedborski, S.; Bencsics, C.; Kang, U.-J. Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease. J. Neurosci. 15:7810-7820; 1995.
61. Lin, L.-F.H.; Mismer, D.; Lile, J.D.; Armes, L.G.; Butler, E.T.; Vannice, J.L.; Collins, F. Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). Science 246:1023-1025; 1989.
62. Lindner, M.D.; Schallert, T. Aging and atropine effects on spatial navigation in the Morris water task. Behav. Neurosci. 102:621-634; 1988.
63. Lindner, M.D.; Gribkoff, V.K. Relationship between performance in the Morris water task, visual acuity, and thermoregulatory function in aged F-344 rats. Behav. Brain Res. 45:45-55; 1991.
64. Lindner, M.D.; Kearns, C.E.; Winn, S.R.; Frydel, B.; Emerich, D.F. Effects of intraventricular encapsulated hNGF-secreting fibroblasts in aged rats. Cell Transplant. 5:205-223; 1996.
65. Lotz, B.; Brooks, B.; Sanjak, M.; Weasler, C.; Roelke, K.; Parnell, J.; Neville, H.; Ringel, S.; Brinkmann, J.; Singh, K.; Burns, D.; Pestronk, A.; Lopate, G.; Florence, J.; Blume, G.; Eliott, J.; Mitsumoto, H.; Levin, K.; Szirony, K.; Caldwell, M.; Bosch, P.; Smith, B.; Verheijde, J.; Carr, S.; Engel, W.K.; Velazquez, L.; Miller, J.; Graves, M.; Sepulveda, L.; Garcia, S.; Smith, R.; Licht, J.; Gillie, E.; Silverman, L.; Olney, R.; Yuen, E.; Melnick, M.; Mass, J.; Bradley, W.; Sharma, K.; Hurtak, L.; Mayor, L.; Olanow, C.W.; Hauser, R.; Malapira, T.; Olanow, E.; Hopkins, L.; Weissman, J.; Pianta, T. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology 46:1244-1249; 1996.
66. MacLennan, J.A.; Vinson, E.N.; Marks, L.; McLaurain, D.L.; Pfiefer, M.; Lee, M. Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system. J. Neurosci. 16:621-630; 1996.
67. Markwell, M.A.K.; Haase, S.M.; Bieber, L.L.; Tolbert, N.E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal. Biochem. 87:206-210; 1978.
68. Martin, J.B. Huntington's disease: New approaches to an old problem. Neurology 34:1059-1072; 1984.
69. Masu, Y.; Wolf, E.; Holtmann, B.; Sendtner, M.; Brem, G.; Thoenen, H. Disruption of the CNTF gene results in motor neuron degeneration. Nature 365:27-32; 1993.
70. Mattson, M.P.; Murrain, M.; Guthrie, P.B.; Kater, S.B. Fibroblast growth factor and glutamate: Opposing roles in the generation and degeneration of hippocampal neuroarchitecture. J. Neurosci. 9:3728-3743; 1989.
71. Mattson, M.P.; Cheng, B.; Smith-Swintosky, V.L. Mechanisms of neurotrophic factor protection against calcium- and free radical-mediated excitotoxic injury: Implications for treating neurodegenerative disorders. Exp. Neurol. 124:89-95; 1993.
72. 2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65:1740-1751; 1995.
73. Montoya, C.P.; Astell, S.; Dunnett, S.B. Effects of nigral and striatal grafts on skilled forelimb use in the rat. Prog. Brain Res. 82:459-466; 1990.
74. Montoya, C.P.; Campbell-Hope, L.J.; Pemberton, K.D.; Dunnett, S.B. The "staircase test": A measure of independent forelimb reaching and grasping abilities in rats. J. Neurosci. Methods 36:219-228; 1991.
75. Olney, J.W. Excitatory amino acids and neuropsychiatric disorders. Biol. Psychiatry 26:505-525; 1989.
76. Oppenheim, R.W.; Prevette, D.; Qin-Wei, Y.; Collins, F.; MacDonald, J. Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor. Science 251: 1616-1618; 1991.
77. Parker, W.D.; Boyson, S.J.; Luder, A.S.; Parks, J.K. Evidence for a defect on NADH: Ubiquinone oxidoreductase (complex I) in Huntington's disease. Neurology 40:1231-1234; 1990.
78. Paxinos, G.; Watson, C. The rat brain in stereotaxic coordinates. Sydney: Academic Press; 1984.
79. Reiner, A.; Albin, D.L.; Anderson, K.D.; D'Amato, C.J.; Penny, J.B.; Young, A.B. Differential loss of striatal projection neurons in Huntington's disease. Proc. Natl. Acad. Sci. USA 85:5733-5737; 1988.
80. Roberts, R.C.; DiFiglia, M. Short- and long-term survival of large neurons in the excitotoxic Iesioned rat caudate nucleus: A light and electron microscopic study. Synapse 3:363-371; 1989.
81. Rosenberg, M.B.; Friedman, T.; Robertson, R.C.; Tuszynski, M.; Wolff, J.A.; Breakefield, X.O.; Gage, F.H. Grafting genetically modified cells to the damaged brain: Restorative effects of NGF expression. Science 242: 1575-1578; 1988.
82. Rothman, S.M. The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J. Neurosci. 5:1483-1490; 1985.
83. Rudge, J.S.; Li, Y.; Pasnikowski, E.M.; Mattsson, K.; Pan, L.; Yancopoulos, G.D.; Wiegand, S.J.; Lindsay, R.M.; Ip, N.Y. Neurotrophic factor receptors and their signal transduction capabilities in rat astrocyles. Eur. J. Neurosci. 6:693-705; 1994.
84. Sagot, Y.; Tan, S.A.; Baetge, E.; Schmalbruch, H.; Kato, A.C.; Aebischer, P. Polymer encapsulated cell lines genetically engineered to release ciliary neurotrophic factor can slow down progressive motor neuronopathy in the mouse. Eur. J. Neurosci. 7:1313-1322; 1995.
85. Sanberg, P.R.; Fibiger, H.C.; Mark, R.R. Body weight and dietary factors in Huntington's disease patients compared with matched controls. Med. J. Aust. 1:407-409; 1981.
86. Sanberg, P.R.; Calderon, S.F.; Giordano, M.; Tew, J.M.; Norman, A.B. The quinolinic acid model of Huntington's disease: Locomotor abnormalities. Exp. Neurol. 105:45-53; 1989.
87. Sanberg, P.R.; Emerich, D.F.; McDermott, P.E.; Frydel, B.R.; Bertino, A.M.; Kaplan, F.A.; Palmatier, M.A.; Christenson, L. Transplantation of polymer-encapsulated bovine adrenal chromaffin cells prevent quinolinic acid induced lesions of the striatum. Soc. Neurosci. Abstr. 17; 1991.
88. SAS Institute Inc. SAS/STAT User's Guide, Version 6, 4th ed., vol. 1. Cary, NC: SAS Institute Inc.; 1989.
89. Schallert, T.; Upchurch, M.; Lobaugh, N.; Farrar, S.B.; Spirduso, W.W.; Gilliam, P.; Vaughn, D.; Wilcox, R.E. Tactile extinction: Distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol. Biochem. Behav. 16:455-462; 1982.
90. Schallert, T.; Upchurch, M.; Wilcox, R.E.; Vaughn, D.M. Posture-independent sensorimotor analysis of interhemispheric receptor asymmetries in neostriatum. Pharmacol. Biochem. Behav. 18:753-759; 1983.
91. Schallert, T.; Jones, T.A.; Norton, D. A clinically relevant unilateral rat model of Parkinsonian akinesia. J. Neural Transplant. Plast. 3:332-333; 1992.
92. Schumacher, J.M.; Short, M.P.; Hyman, B.T.; Breake-field, X.O.; Isacson, O. Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids. Neuroscience 45:561-570; 1991.
93. + pump necessary for NGF mediated neuronal survival? J. Neurosci. 8:458-462; 1988.
94. Sendtner, M.; Kreutzberg, G.W.; Thoenen, H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345:440-341; 1990.
95. Sendtner, M.; Schmalbruch, H.; Stockli, K.A.; Carroll, P.; Kreutzberg, G.W.; Thoenen, H. Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronpathy. Nature 358:502-504; 1992.
96. Stanhope, K.J.; Mclenachan, A.P.; Dourish, C.T. Dissociation between cognitive and motor/motivational deficits in the delayed matching to position test: Effects of scopolamine, 8-OH-DPAT and EAA antagonists. Psychopharmacology (Berlin) 122:268-280; 1995.
97. Stockli, K.A.; Lottspeich, F.; Sendtner, M.; Masiakowski, P.; Carrol, P.; Gotz, R.; Lindholm, D.; Thoenen, H. Molecular cloning, expression, and regional distribution of rat ciliary neurotrophic factor. Nature 342:920-923; 1989.
98. Stockli, K.A.; Lillien, L.E.; Naher-Noe, M.; Breitfeld, G.; Hughes, R.A.; Raff, M.C.; Thoenen, H.; Sendtner, M. Regional distribution, developmental changes and cellular localization of CNTF-mRNA and protein in the rat brain. J. Cell Biol. 115:447-459; 1991.
99. Tulipan, N.; Luo, S.-Q.; Allen, G.; Whetsell, W.O. Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage. Exp. Neurol. 102:325-332; 1988.
100. Ulenkate, H.J.L.M.; Kaal, E.C.A.; Jennekens, F.G.I. Ciliary neurotrophic factor induces hypophagia, hypodipsia, and diminished weight gain in young adult rats. Neurosci. Res. Commun. 16:67-74; 1995.
101. Wallace, D.C. Mitochondrial genetics: A paradigm for aging and degenerative diseases? Science 256:628-632; 1992.
102. Wen, T.C.; Matsuda, S.; Yoshimura, H.; Kawabe, T.; Sakanaka, M. Ciliary neurotrophic factor prevents ischemiainduced learning disability and neuronal loss in gerbils. Neurosci. Lett. 191:55-58; 1995.
103. Winn, S.R.; Hammang, J.P.; Emerich, D.F.; Lee, A.; Palmiter, R.D.; Baetge, E.E. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons. Proc. Natl. Acad. Sci. USA 91:23-28; 1994.
104. Winn, S.R.; Lindner, M.D.; Francis, J.M.; Haggett, G.; Greco, C.; Frydel, B.; Emerich, D.F. Encapsulated engineered cells continue to secrete human nerve growth factor for over one year in rat ventricles: A behavioral and anatomical analysis. Exp. Neurol. 140:126-138; 1996.