scholarly journals Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases

2021 ◽  
Author(s):  
Anita Monteverdi ◽  
Fulvia Palesi ◽  
Alfredo Costa ◽  
Paolo Vitali ◽  
Anna Pichiecchio ◽  
...  

Brain pathologies are based on microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients excitation/inhibition profiles on neurodegenerative diseases including Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. In this work we used a simulation platform, The Virtual Brain, to simulate brain dynamics in healthy controls and in Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis patients. The brain connectome and functional connectivity were extracted from 3T-MRI scans and The Virtual Brain nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the excitatory/inhibitory balance. The integration of cerebro-cerebellar loops improved the correlation between experimental and simulated functional connectivity, and hence The Virtual Brain predictive power, in all pathological conditions. The Virtual Brain biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in Alzheimer's disease and stronger NMDA (N-methyl-D-aspartate) receptor-dependent excitation in Amyotrophic Lateral Sclerosis. These physio-pathological parameters allowed an advanced analysis of patients' state. In backward regressions, The Virtual Brain parameters significantly contributed to explain the variation of neuropsychological scores and, in discriminant analysis, the combination of The Virtual Brain parameters and neuropsychological scores significantly improved discriminative power between clinical conditions. Eventually, cluster analysis provided a unique description of the excitatory/inhibitory balance in individual patients. In aggregate, The Virtual Brain simulations reveal differences in the excitatory/inhibitory balance of individual patients that, combined with cognitive assessment, can promote the personalized diagnosis and therapy of neurodegenerative diseases.

2018 ◽  
Vol 13 (3) ◽  
pp. 651-659 ◽  
Author(s):  
Jordi A. Matías-Guiu ◽  
María Nieves Cabrera-Martín ◽  
María Valles-Salgado ◽  
Teresa Rognoni ◽  
Lucía Galán ◽  
...  

2011 ◽  
Vol 3 (3) ◽  
pp. 242-247 ◽  
Author(s):  
A. Yamanami-Irioka ◽  
T. Uchihara ◽  
T. Endo ◽  
T. Irioka ◽  
M. Watanabe ◽  
...  

Author(s):  
Edward Poluyi ◽  
Eghosa Morgan ◽  
Charles Poluyi ◽  
Chibuikem Ikwuegbuenyi ◽  
Grace Imaguezegie

Abstract Background Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives This review will discuss the available literatures linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods Given the complexity of this subject, a realist review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways. Conclusion mTBI constitutes majority of brain injuries. However, studies have focused mostly on moderate-to-severe TBI as highlighted above with inconclusive and paucity of studies linking concussion and neurodegenerative disorders. Although, it is highly probable that repetitive concussion (mTBI) and subconcussive head injuries may be risk factors for ALS) and AD from this review. It will be imperative therefore to conduct more research with a focus on mTBI and its association with ALS and AD.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Li Shu ◽  
Qiying Sun ◽  
Yuan Zhang ◽  
Qian Xu ◽  
Jifeng Guo ◽  
...  

C9orf72is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasian populations. However, the relationship betweenC9orf72repeats and Alzheimer’s disease (AD) was not clear. Additionally, there were few articles assessingC9orf72in other ethnicities with ALS. In this meta-analysis, we aimed to investigate the relationship betweenC9orf72repeat expansions (≥30 repeats) and intermediate repeat copies (20–29 repeats) and AD or ALS. The results suggested positive correlations betweenC9orf72repeat expansions and the risk of Alzheimer’s disease (OR = 6.36, 95% CI = 3.13–12.92, andp<0.00001), while intermediate repeat copies ofC9orf72gene were not associated with the risk of the disease.C9orf72repeat expansions were positively correlated with the risk of familial and sporadic ALS (OR = 293.25, 95% CI = 148.17–580.38, andp<0.00001; OR = 35.57, 95% CI = 19.61–64.51, andp<0.00001). There was a positive correlation between the gene variations and ALS risk among Caucasians and Asians (OR = 57.56, 95% CI = 36.73–90.22, andp<0.00001; OR = 6.35, 95% CI = 1.39–29.02, andp=0.02).


Author(s):  
Nicolas Ruffini ◽  
Susanne Klingenberg ◽  
Susann Schweiger ◽  
Susanne Gerber

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.


2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Marco Orsini ◽  
Osvaldo J.M. Nascimento ◽  
Andre P.C. Matta ◽  
Carlos Henrique Melo Reis ◽  
Olivia Gameiro De Souza ◽  
...  

Thanks to the development of several new researches, the lifetime presented a significant increase, even so, we still have many obstacles to overcome − among them, manage and get responses regarding neurodegenerative diseases. Where we are in the understanding of neuroprotection? Do we really have protective therapies for diseases considered degeneratives such as amyotrophic lateral sclerosis and its variants, Parkinson’s disease, Alzheimer’s disease and many others? Neuroprotection is defined by many researches as interactions and interventions that can slow down or even inhibit the progression of neuronal degeneration process. We make some considerations on this <em>neuroprotective</em> <em>effect</em>.


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