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EFFECTS OF NGF AND FETAL CELL TRANSPLANTS ON SPATIAL LEARNING AFTER INTRADENTATE ADMINISTRATION OF COLCHICINE
Citation:
Barone, S., P. Tandon, J. McGinity, AND H. Tilson. EFFECTS OF NGF AND FETAL CELL TRANSPLANTS ON SPATIAL LEARNING AFTER INTRADENTATE ADMINISTRATION OF COLCHICINE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/063 (NTIS PB92150770).
Description:
This study was performed to assess the effects of NGF infusion alone or in combination with fetal hippocampal transplants on recovery of function after damage to hippocampal dentate granule cells. Two groups of male Fischer-344 rats received bilateral infusions of colchicine (COLCH; 2.5 ug/site) or artificial cerebrospinal fluid (ACSF; 0.5 ul) through chronic indwelling cannulae into the dentate gyrus. Following treatment with COLCH, unilateral intracerebroventricular (ICV) cannula was implanted. One week later, when animals were tested in activity chambers for 60 min, COLCH-treated rats showed a significant increase in spontaneous locomotor activity. wo weeks after COLCH treatment, animals were assigned to various post-treatment groups and received 1.0 ul of rat fetal hippocampal cell suspensions (ED-17 or 18) or Earle's basic salt solution in the same site as previous hippocampal infusions. Modified Alzet mini-osmotic pumps (0.25 ul/hr) containing NGF (10 ng/ul) or ACSF with cytochrome C (20 ng/ul) were implanted subcutaneously and attached to the previously implanted ICV cannulae. Animals were tested in a Morris water maze task starting 6 or 12 weeks post-COLCH. At 6 weeks post-lesion. COLCH lesions significantly impaired acquisition. GF treatment ameliorated this COLCH-induced behavioral deficit 6 weeks post-lesion while the presence of transplants did not ameliorate the COLCH-induced learning deficit. Transplant/NGF-treated rats performed better than both COLCH-lesioned rats with or without transplants. OLCH-induced behavioral deficits were not ameliorated by NGF or transplants at 12 weeks post-lesion. Morphological examination performed after behavioral testing confirmed the presence of viable transplants and COLCH-induced granule cell loss. xogenous NGF infusions had no effect on the morphological measures taken. hese data demonstrate a time-dependent facilitative effect of exogenously applied NGF on functional deficiencies produced by experimentally induced neurodegeneration in the dentate gyrus of the hippocampus.