Induction of Memory and Cortical Cholinergic Neurochemical Recovery with Combine Fetal Transplantation and GM1 Treatments in Rats with Lesions of the NBM

Abstract

Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilateral nucleus basalis of Meynert (nbM) lesions; 10 additional animals served as sham controls. Eight to ten days later, subjects with lesions received either fetal cholinergic transplants implanted within the ipsilateral (relative to the lesion) frontal cortex or control transplant surgeries. Lesioned animals with and without transplants were then treated with GM1 (20 mg/kg, i.p.) for either 0,1 or 10 days and were then trained and tested for 72-hour retention of passive avoidance. Results indicated that the lesion produced a significant impairment on this task. Transplant therapy combined with GM1 for 10 days yielded a significant reversal of this deficit. GM1 injections continued once per week for 4 weeks for half the lesioned animals in the transplant and no-transplant 10-day conditions. During a 6-month period, all subjects were assessed on two additional memory tasks (complex spatial discrimination and delayed spatial alternation). In general, there was no indication of a lesion, transplant, GM1, or transplant × GM1 effect on these tasks. Approximately 7.5 months after transplants, subjects were sacrificed and their frontal cortices examined for choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activity. Only lesioned subjects with transplants which were given sustained GMl treatment (i.e., 10 days plus weekly injections for 4 weeks) showed significant attenuations of lesion-induced CAT and AChE depletions. These data suggest that a combined treatment strategy of fetal transplant plus GM1 is capable of reversing nbM lesion-induced memory and neurochemical deficits in an animal model of the cholinergic deficits in Alzheimer's disease.

Behavioral effects of GM1 ganglioside treatment and intrahippocampal septal grafts in rats with fimbria-fornix lesions

“…The partial recovery of cognitive function observed in our experiment in lesioned rats given grafts and treated with GM1 is in line with data from other studies that also investigated the interaction between grafts and ganglioside treatment, with, however, different lesion paradigms (Nishino et al 1990;Santucci et al 1993;Slavin et al 1988). For instance, Santucci et al (1993) found a complete recovery of function (retention of a passive avoidance task) from Nucleus baralis magnocellularis (NBM) lesion-induced deficits, but only in rats receiving intracortical grafts of basal forebrain tissue and being treated with GM1. In these rats, the authors also found that, 6 months after GM1 treatment, the cortical Choline-acetyltransferase (ChAT) activity had been completely normalized in contrast to that found in both the saline-treated grafted rats and the GM1-treated lesion-only rats.…”

Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat

“…The use of various growth factors to modify the microenvironment after transplantation has been shown to improve graft survival and function. [13,30,41,56] After experimental brain injury in rats, nerve growth factor (NGF) receptors have been shown to decrease, [27] whereas NGF infusions have recently been shown to improve cognitive outcome. [43] The histological correlates and cellular mechanisms that underlie these improvements have yet to be identified.…”

Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat

“…[2,21,23,37,38] The use of various growth factors to modify the microenvironment after transplantation has been shown to improve graft survival and function. [13,30,41,56] After experimental brain injury in rats, nerve growth factor (NGF) receptors have been shown to decrease,[27] whereas NGF infusions have recently been shown to improve cognitive outcome.[43] The histological correlates and cellular mechanisms that underlie these improvements have yet to be identified.The lateral fluid-percussion model of brain injury in the rat results in well-characterized outcomes that reproduce many components of human head injury. [11,29,36] Previous studies have demonstrated that fetal neural transplants survive when grafted in the acute posttraumatic period in this injury model.…”

“…[2,21,23,37,38] The use of various growth factors to modify the microenvironment after transplantation has been shown to improve graft survival and function. [13,30,41,56] After experimental brain injury in rats, nerve growth factor (NGF) receptors have been shown to decrease,[27] whereas NGF infusions have recently been shown to improve cognitive outcome.…”

“…[13,30,41,56] After experimental brain injury in rats, nerve growth factor (NGF) receptors have been shown to decrease, [27] whereas NGF infusions have recently been shown to improve cognitive outcome. [43] The histological correlates and cellular mechanisms that underlie these improvements have yet to be identified.…”