Differential activation of transcription factor NF -lCB in brainstem and medial septum cholinergic neurons in an Alzheimer's Disease rat model
Zywicke, Holly A.
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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.