The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.

Abstract:

:Six Rhesus monkeys between 24 and 29 years of age received unilateral transections of the fornix. Three monkeys then received intraventricular transplants of polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three monkeys received identical grafts except the cells were not modified to secrete hNGF. Monkeys receiving the fornix transection and control grafts displayed extensive reductions in the number of choline acetyltransferase- (57-75%) and p75 NGF receptor- (53%) immunoreactive medial septal neurons ipsilateral to the lesion/implant. In contrast, monkeys receiving transplants of encapsulated hNGF-secreting cells display only a modest loss of choline acetyltransferase- (0-36%) and p75 NGF receptor-(7-22.4%) immunoreactive septal neurons. Additionally, all monkeys receiving the hNGF-secreting implants, but none receiving control implants, displayed robust sprouting of cholinergic fibers within the septum ipsilateral to the transplant. Just prior to sacrifice, the capsules were retrieved and found to contain viable BHK cells releasing biologically relevant levels of hNGF. These data demonstrate that hNGF can provide trophic and tropic influences to aged primate basal forebrain neurons undergoing lesion-induced degeneration, supporting the contention that hNGF may prevent the degeneration of basal forebrain neurons in Alzheimer disease.

authors

Kordower JH,Winn SR,Liu YT,Mufson EJ,Sladek JR Jr,Hammang JP,Baetge EE,Emerich DF

doi

10.1073/pnas.91.23.10898

subject

Has Abstract

pub_date

1994-11-08 00:00:00

pages

10898-902

issue

23

eissn

0027-8424

issn

1091-6490

journal_volume

91

pub_type

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