Differential activation of transcription factor NF -lCB in brainstem and medial septum cholinergic neurons in an Alzheimer's Disease rat model
Loading...
Authors
Zywicke, Holly A.
Issue Date
2000
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Neurodegenerative disorders cause progressive decline in neurological functions
and cognitive abilities. Physical and mental deficiencies in each disorder result from
damage restricted to specific cells, areas and/or circuits within the brain. Alzheimer's
Disease (AD), characterized by progressive cognitive decline resulting in severe
dementia, results partially from degeneration of neurons that process the neurotransmitter
acetylcholine. Cholinergic neurons are located in two brain regions: the brainstem and the
basal forebrain system. Initial examination of cholinergic brainstem and medial septum
neurons revealed a selective vulnerability between the two populations in both AD and its
corresponding rat model. Brainstem cholinergic neurons survive much better than those
of the medial septum. The cause of this differential cholinergic vulnerability is unknown.
An important question is whether transcription factor NF-icB, which mediates stress
response, is involved in increased survival ofbrainstem cholinergic neurons. If
NF-icB is neuroprotective, a probable hypothesis is that brainstem neurons have higher
levels of activated NF-icB when compared to medial septum cholinergic neurons.
Dissected brainstem and medial septum regions from a 3-nitropropionic acid (3-NP)
induced AD rat model were dually stained with fluorescent antibodies specific for choline
acetyltransferase and NF-icB. Results showed a high level of inactive and active NF-icB
in both brainstem and medial septum of AD rats. In contrast, in control rats, the level of
NF-icB in brainstem and medial septum populations was substantially lower.
Significantly, in AD rats, brainstem neurons had more overall NF-icB than medial septum
cholinergic neurons. Further molecular insight into NF-icB activation may advance
understanding of the process underlying AD.
With honors.
With honors.
Description
vi, 44 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.