scholarly journals Effects of Inducing Gamma Oscillations in Hippocampal Subregions DG, CA3, and CA1 on the Potential Alleviation of Alzheimer’s Disease-Related Pathology: Computer Modeling and Simulations

Entropy ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 587
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Gamma Oscillations ◽  
Control Model ◽  
Transfer Entropy ◽  
Ca1 Region ◽  
Pathological Model ◽  
The One

The aim of this study was to evaluate the possibility of the gamma oscillation function (40–130 Hz) to reduce Alzheimer’s disease related pathology in a computer model of the hippocampal network dentate gyrus, CA3, and CA1 (DG-CA3-CA1) regions. Methods: Computer simulations were made for a pathological model in which Alzheimer’s disease was simulated by synaptic degradation in the hippocampus. Pathology modeling was based on sequentially turning off the connections with entorhinal cortex layer 2 (EC2) and the dentate gyrus on CA3 pyramidal neurons. Gamma induction modeling consisted of simulating the oscillation provided by the septo-hippocampal pathway with band frequencies from 40–130 Hz. Pathological models with and without gamma induction were compared with a control. Results: In the hippocampal regions of DG, CA3, and CA1, and jointly DG-CA3-CA1 and CA3-CA1, gamma induction resulted in a statistically significant improvement in terms of increased numbers of spikes, spikes per burst, and burst duration as compared with the model simulating Alzheimer’s disease (AD). The positive maximal Lyapunov exponent was negative in both the control model and the one with gamma induction as opposed to the pathological model where it was positive within the DG-CA3-CA1 region. Gamma induction resulted in decreased transfer entropy in accordance with the information flow in DG → CA3 and CA3 → CA1. Conclusions: The results of simulation studies show that inducing gamma oscillations in the hippocampus may reduce Alzheimer’s disease related pathology. Pathologically higher transfer entropy values after gamma induction returned to values comparable to the control model.

scholarly journals Computer Model of Synapse Loss During an Alzheimer’s Disease-like Pathology in Hippocampal Subregions DG, CA3 and CA1—the Way to Chaos and Information Transfer

Entropy ◽  
2019 ◽  
Vol 21 (4) ◽  
pp. 408 ◽  
Author(s):  
Świetlik ◽  
Białowąs ◽  
Moryś ◽  
Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lyapunov Exponent ◽  
Information Flow ◽  
Shannon Entropy ◽  
Control Model ◽  
Maximal Lyapunov Exponent ◽  
Synapse Loss ◽  
Entropy Transfer ◽  
Pathological Model

The aim of the study was to compare the computer model of synaptic breakdown in an Alzheimer’s disease-like pathology in the dentate gyrus (DG), CA3 and CA1 regions of the hippocampus with a control model using neuronal parameters and methods describing the complexity of the system, such as the correlative dimension, Shannon entropy and positive maximal Lyapunov exponent. The model of synaptic breakdown (from 13% to 50%) in the hippocampus modeling the dynamics of an Alzheimer’s disease-like pathology was simulated. Modeling consisted in turning off one after the other EC2 connections and connections from the dentate gyrus on the CA3 pyramidal neurons. The pathological model of synaptic disintegration was compared to a control. The larger synaptic breakdown was associated with a statistically significant decrease in the number of spikes (R = −0.79, P < 0.001), spikes per burst (R = −0.76, P < 0.001) and burst duration (R = −0.83, P < 0.001) and an increase in the inter-burst interval (R = 0.85, P < 0.001) in DG-CA3-CA1. The positive maximal Lyapunov exponent in the control model was negative, but in the pathological model had a positive value of DG-CA3-CA1. A statistically significant decrease of Shannon entropy with the direction of information flow DG->CA3->CA1 (R = −0.79, P < 0.001) in the pathological model and a statistically significant increase with greater synaptic breakdown (R = 0.24, P < 0.05) of the CA3-CA1 region was obtained. The reduction of entropy transfer for DG->CA3 at the level of synaptic breakdown of 35% was 35%, compared with the control. Entropy transfer for CA3->CA1 at the level of synaptic breakdown of 35% increased to 95% relative to the control. The synaptic breakdown model in an Alzheimer’s disease-like pathology in DG-CA3-CA1 exhibits chaotic features as opposed to the control. Synaptic breakdown in which an increase of Shannon entropy is observed indicates an irreversible process of Alzheimer’s disease. The increase in synapse loss resulted in decreased information flow and entropy transfer in DG->CA3, and at the same time a strong increase in CA3->CA1.

scholarly journals Computer Modeling of Alzheimer’s Disease—Simulations of Synaptic Plasticity and Memory in the CA3-CA1 Hippocampal Formation Microcircuit

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1909
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Computer Modeling ◽  
Hippocampal Formation ◽  
Pyramidal Cells ◽  
Control Model ◽  
Pathological Model ◽  
Ca3 Pyramidal Cells ◽  
And Control

This paper aims to present computer modeling of synaptic plasticity and memory in the CA3-CA1 hippocampal formation microcircuit. The computer simulations showed a comparison of a pathological model in which Alzheimer’s disease (AD) was simulated by synaptic degradation in the hippocampus and control model (healthy) of CA3-CA1 networks with modification of weights for the memory. There were statistically higher spike values of both CA1 and CA3 pyramidal cells in the control model than in the pathological model (p = 0.0042 for CA1 and p = 0.0033 for CA3). A similar outcome was achieved for frequency (p = 0.0002 for CA1 and p = 0.0001 for CA3). The entropy of pyramidal cells of the healthy CA3 network seemed to be significantly higher than that of AD (p = 0.0304). We need to study a lot of physiological parameters and their combinations of the CA3-CA1 hippocampal formation microcircuit to understand AD. High statistically correlations were obtained between memory, spikes and synaptic deletion in both CA1 and CA3 cells.

scholarly journals Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Possible Therapeutic Role of Curcumin

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 248
Author(s):  
Ryszard Pluta ◽  
Wanda Furmaga-Jabłońska ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Ischemia ◽  
Tau Protein ◽  
Pyramidal Neurons ◽  
Infarct Volume ◽  
Well Being ◽  
Biological Properties ◽  
Ischemic Brain ◽  
Ca1 Region

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer’s disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.

scholarly journals Overexpression of HIF-2α in Alzheimer's disease Resilient Patients

2020 ◽  
Author(s):  
Vivianne Mitri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Amyloid Plaques ◽  
Stratum Radiatum ◽  
Alzheimers Disease ◽  
Cytoplasmic Staining ◽  
Neuronal Nuclei ◽  
Hypoxic Conditions

Alzheimers disease (AD) Resilient individuals are characterized by having a degree of amyloid plaques at level with that of demented individuals, but a reduced amount of abnormal neurofibrillary protein tangles (NFTs). NFTs, also known to be upregulated under hypoxic conditions, become clinically relevant when involved in the stratum radiatum. In this paper, we show this region and more to have significant increases of hypoxic adaptive protein, HIF-2α, within AD resilient cases. Pericyte staining was present in the stratum lacunosum and radiatum of all cases affected by AD pathology (n = 4) but in AD resilient cases were increased by 12-fold (n=3) p<.0001. No staining was detected in normal cases (n=2). HIF-2α was also only present in hippocampal neuronal nuclei of AD resilient cases, including the dentate gyrus and CA1. Cytoplasmic staining of pyramidal neurons within the subiculum was seen in all cases affected by AD pathology. The intensity of HIF-2α appears to be specific to known regions of protection in AD resilience and to increase on a gradient that corresponds to protection against dementia. These results also highlight the stratum lacunosum and radiatum as regions critically impacted by hypoxic insult among AD cases.

scholarly journals Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

scholarly journals Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer’s disease pathology

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline A. Wilson ◽  
Sarah Fouda ◽  
Shuzo Sakata
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Gamma Oscillations ◽  
Cortical Region ◽  
Sensory Stimuli ◽  
Beneficial Effects ◽  
Amyloid Load ◽  
5Xfad Mice ◽  
Frontal Cortical Region

Abstract Neuronal activity can modify Alzheimer’s disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer’s disease pathology can depend on the induction mechanisms of cortical gamma oscillations.

Sign in / Sign up

Export Citation Format

Share Document