Intraventricular implant of encapsulated CNTF-secreting fibroblasts ameliorates motor deficits in aged rats.
The impact of intraventricular ciliary neurotrophic factor (CNTF) on motor function in aged rats was evaluated. Spontaneous locomotion and motor coordination were quantified in young (5-6 months) and aged (24-25 months) rats. Relative to young animals, aged rats were significantly less active, fell more rapidly from a rotating rod, and were unable to maintain their balance on a wooden beam. Aged animals received bilateral intraventricular implants of polymer-encapsulated fibroblasts that were genetically modified to secrete CNTF. Controls received either no implant or capsules loaded with mock transfected cells. One month after implantation the aged animals that received CNTF implants were significantly more active and were improved on the rotorod and beam balance tests. The improvement in performance on the rotorod and beam balance tests was dependant on the task difficulty and dissipated at higher rotations (rotorod) and smaller beam widths (beam balance). No recovery was seen in aged animals receiving control implants. Postmortem removal of the encapsulated cells confirmed that they continued to secrete CNTF. These data are the first to suggest that intracerebral delivery of CNTF might be useful for slowing or reversing age-related changes in motor function.
Emerich
Dwaine F
DF
InCytu, Inc., Lincoln, Rhode Island 02865, USA. ED3FJM@aol.com
Thanos
Christopher G
CG
Sanberg
Paul R
PR
D000367:Age Factors; D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D002460:Cell Line; D002552:Cerebral Ventricles / Q000378:metabolism / Q000601:surgery*; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D009043:Motor Activity; D004856:Postural Balance; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013997:Time Factors; D014162:Transfection
D020934:Ciliary Neurotrophic Factor