Alzheimer’s Disease as a Result of Stimulus Reduction in a GABA-A-Deficient Brain: A Neurocomputational Model

Abstract

Several research studies point to the fact that sensory and cognitive reductions like cataracts, deafness, macular degeneration, or even lack of activity after job retirement, precede the onset of Alzheimer’s disease. To simulate Alzheimer’s disease earlier stages, which manifest in sensory cortices, we used a computational model of the koniocortex that is the first cortical stage processing sensory information. The architecture and physiology of the modeled koniocortex resemble those of its cerebral counterpart being capable of continuous learning. This model allows one to analyze the initial phases of Alzheimer’s disease by “aging” the artificial koniocortex through synaptic pruning, by the modification of acetylcholine and GABA-A signaling, and by reducing sensory stimuli, among other processes. The computational model shows that during aging, a GABA-A deficit followed by a reduction in sensory stimuli leads to a dysregulation of neural excitability, which in the biological brain is associated with hypermetabolism, one of the earliest symptoms of Alzheimer’s disease.

NetTDP: permutation-based true discovery proportions for differential co-expression network analysis

“…Cell-substrate junction (GO:0030055) is also discovered by John et al [37] related to AD. Mariana et al [38] claimed that Alzheimer's disease is a result of stimulus reduction in a GABA-A-deficient brain, which supports positive regulation of response to stimulus (GO:0048584) and response to extracellular stimulus (GO:0009991) may play important roles in Alzheimer's disease.…”

Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods

“…γ-Aminobutyric acid (GABA) is a major neurotransmitter, which dominates inhibitory conduction . The malfunction of GABAergic neurons is often associated with neurodevelopmental and neurodegenerative disorders, such as epilepsy, Huntington’s disease, Alzheimer’s disease, etc. − There have been attempts to regenerate GABAergic neurons through stem cells based methods, enabling the study of pathogenesis and therapeutics. , In particular, many studies program embryonic stem cells (ESCs) or induce pluripotent stem cells (iPSCs) to derive GABAergic neurons by genetic engineering technology. In comparison, neural stem cells (NSCs) may be better because they are distributed in the central nervous system and capable to terminally differentiate into neurons and glial cells .…”

Ginger, a Possible Candidate for the Treatment of Dementias?

“…Aguiar-Furucho et al [ 45 ] demonstrated the beneficial effects on the consumption of terpenoid-based nutrients, such as ginger, and foods containing fisetin, such as strawberries, tomatoes, oranges, and cucumbers. To investigate the AD symptoms, the authors used a computational model of koniocortex, a region of cerebral cortex related to the processing of sensory information.…”

“…Aguiar-Furucho et al [45] demonstrated the beneficial effects on the consump terpenoid-based nutrients, such as ginger, and foods containing fisetin, such as str The potential effect of zerumbone as a cholinesterase inhibitor was evaluated by Hwang et al, in vitro by enzyme assays, in silico docking, and simulation of absorption, distribution, metabolism, excretion, and toxicity. The results of the study demonstrated that zerumbone inhibited AChE and BChE, assessed by an anticholinesterase activity assay and measured by zerumbone kinetics.…”