TITLE:
Intermittent vs Continuous Administration of Nerve Growth Factor to Injured Medial Septal Cholinergic Neurons in Rat Basal Forebrain
AUTHORS:
Kenneth E. Miller, Gregory E. Frierdich, Robert H. Dillard, Robert H. Soriano, Dikla G. Roufa
KEYWORDS:
Nerve Growth Factor, Medial Septal Nucleus, Choline Acetyltransferase, Alzheimer’s, Fimbria, Fornix
JOURNAL NAME:
Neuroscience and Medicine,
Vol.5 No.2,
April
30,
2014
ABSTRACT: Many medial septal neurons of the basal forebrain
are dependent on nerve growth factor (NGF) from the hippocampus for survival
and maintenance of a cholinergic phenotype. When deprived of their source of
NGF by axotomy, medial septal neuronal cell bodies atrophy and lose their cholinergic
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 NGF 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, NGF activity diminished
greatly 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 NGF was dose dependent and the ED50 for NGF injection was
determined to be 14.08 μg/ml compared to 27.60 μg/ml for NGF infusion.
Intermittent injections at varying intervals were evaluated with 30 μg/ml NGF
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 NGF. NGF
administration has been suggested as a therapy for AD. The results of these studies
continue to highlight the need for NGF stability within the delivery system and
AD patient CSF, the choice of delivery system, frequency of administration, and
the NGF dose for maintaining basal forebrain cholinergic neurons during AD.