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Intermittent vs Continuous Administration of Nerve g.owth Factor to Injured Medial Septal Cholinerg.c Neurons in Rat Basal Forebrain

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Neuroscience & Medicine 2014年第2期5卷 109-118页

作者： Kenneth E. Miller g.eg.ry E. Frierdich Robert H. Dillard Robert H. Soriano dikla g. roufa Department of Anatomy and Cell Biolog. Oklahoma State University Center for Health Sciences Tulsa USA

Many medial septal neurons of the basal forebrain are dependent on nerve g.owth factor (Ng.) from the hippocampus for survival and maintenance of a cholinerg.c phenotype. When deprived of their source of Ng. by axotomy, medial septal neuronal cell bodies atrophy and lose their cholinerg.c markers. This is similar to what is observed in the basal forebrain during.Alzheimer’s disease (AD). In the present study, medial septal neurons were axotomized in female rats by way of a fimbria/fornix lesion. For fourteen days following.axotomy, varying.Ng. doses (1 - 250 μg.ml) were administered to the lateral cerebral ventricle with either mini-osmotic infusion or daily injection. The responsiveness of medial septal neurons was evaluated with choline acetyltransferase immunohistochemistry. Within the mini-osmotic pumps, Ng. activity diminished g.eatly during.the first five days of implantation, but increased dramatically in the CSF after five days of infusion. The responsiveness of medial septal neurons to Ng. was dose dependent and the ED50 for Ng. injection was determined to be 14.08 μg.ml compared to 27.60 μg.ml for Ng. infusion. Intermittent injections at varying.intervals were evaluated with 30 μg.ml Ng. over a fourteen-day time period (2, 3, 6, or 12 injections). No differences occurred in the number of choline acetyltransferase neurons from rats that received weekly injections to those that received daily injections of Ng.. Ng. administration has been sug.ested as a therapy for AD. The results of these studies continue to hig.lig.t the need for Ng. stability within the delivery system and AD patient CSF, the choice of delivery system, frequency of administration, and the Ng. dose for maintaining.basal forebrain cholinerg.c neurons during.AD.

关键词： Nerve g.owth Factor Medial Septal Nucleus Choline Acetyltransferase Alzheimer’s Fimbria Fornix

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