Title:Oxidative Damage of Proteins Precedes Loss of Cholinergic Phenotype in
the Septal Neurons of Olfactory Bulbectomized Mice
Volume: 18
Issue: 14
关键词:
嗅球切除术、胆碱能神经元、中隔、氧化应激、羰基、阿尔茨海默病。
摘要:
Background: The development of cholinergic deficit is considered an early sign of a
number of pathological conditions, including Alzheimer’s disease. Cholinergic dysfunction underlies
cognitive decline associated with both normal aging and Alzheimer’s disease.
Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons
using an olfactory bulbectomy model.
Methods: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after
that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic
indices as well as the indices of oxidative stress were studied using immunohistochemistry,
western blot and ELISA. Gene expression was studied using RT-qPCR.
Results: The experimental treatment was followed by impaired learning of a standard spatial task
in a water maze. This was associated with a decrease in the number of cells containing choline
acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower
ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular
ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared
to sham-operated animals. These alterations were preceded by the accumulation of protein-bound
carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was
not detected.
Conclusion: We assume that in olfactory bulbectomy model, oxidative damage of proteins may
cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that
cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible
for the appearance of early cognitive decline in Alzheimer’s disease.