Effect of acetylcholine deficiency on neural oscillation in a brainstem-thalamus-cortex neurocomputational model related with Alzheimer’s disease

Abstract

Previous works imply that involving brainstem in neuropathological studies of Alzheimer’s disease (AD) is of clinically significant. This work constructs a comprehensive neural mass model for cholinergic neuropathogenesis that involves brainstem, thalamus and cortex, wherein how acetylcholine deficiency in AD affects neural oscillation of the model output is systematically explored from the perspective of neurocomputation. By decreasing synapse connectivity parameters in direct cholinergic pathway from brainstem to thalamus or in indirect glutamatergic synapse pathway from cortex to brainstem to mimic the pathological condition of reduced acetylcholine release in patients with AD, the property of neural oscillation in this model is numerically investigated by means of power spectrum in frequency domain and amplitude distribution in time domain. Simulated results demonstrate that decreasing synapse connectivity whether in the direct cholinergic pathway or in the indirect glutamatergic synapse pathway can alter the neural oscillation significantly in three aspects: it induces an obvious decrease of dominant frequency; it leads to a degraded rhythmic activity in the alpha frequency band as well as an enhanced rhythmic activity in the theta frequency band; it results in reduced oscillation amplitude of the model output. These results are agreement with the characteristic of electrophysiological EEG measurement recorded in AD, especially support the hypothesis that cholinergic deficiency is a promising pathophysiological origin of EEG slowing in AD. Our analysis indicates that targeting the cholinergic system may have potential prospects in early diagnosis and treatment of AD.

Exploring Cannabis sativa L for Anti-Alzheimer Potential: An extensive Computational Study including Molecular Docking, Molecular Dynamics, and ADMET Assessments

“…Subsequently, structural optimization was carried out using the MMFF94 force eld, with the steepest Descent methodology [54]-[56], available in Avogadro software [57]. Afterward, using AutoDockTools-1.5.6 [39], PDBQT les for the investigated structures were produced, serving as docking input data [58].…”

“…Moreover, Alzheimer's disease is associated with decreased levels of acetylcholine due to intensive loss of cholinergic neurons [39]. Since acetylcholine is a neurotransmitter implicated in memory and learning, its hydrolysis leads to an altered neurotransmission process in Alzheimer's disease patients.…”