Dynamical Characteristics of State Transition Defined by Neural Activity of Phase in Alzheimer’s Disease

2021 ◽  
pp. 46-54
Author(s):  
Sou Nobukawa ◽  
Takashi Ikeda ◽  
Mitsuru Kikuchi ◽  
Tetsuya Takahashi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neural Activity ◽  
State Transition ◽  
Dynamical Characteristics

scholarly journals Cytokine signaling convergence regulates the microglial state transition in Alzheimer’s disease

2021 ◽  
Author(s):  
Shun-Fat Lau ◽  
Amy K. Y. Fu ◽  
Nancy Y. Ip
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
State Transition ◽  
Cytokine Signaling ◽  
Interleukin 33 ◽  
Beneficial Effects ◽  
Activated State ◽  
Therapeutic Development ◽  
Functional States

AbstractGenetic analyses have revealed the pivotal contribution of microglial dysfunctions to the pathogenesis of Alzheimer’s disease (AD). Along AD progression, the accumulation of danger-associated molecular patterns (DAMPs) including beta-amyloid and hyperphosphorylated tau continuously stimulates microglia, which results in their chronic activation. Chronically activated microglia secrete excessive pro-inflammatory cytokines, which further regulate microglial responses towards DAMPs. This has spurred longstanding interest in targeting cytokine-induced microglial responses for AD therapeutic development. However, the cytokine-induced microglial state transition is not comprehensively understood. Cytokines are assumed to induce microglial state transition from a resting state to an activated state. However, recent evidence indicate that this microglial state transition involves multiple sequential functional states. Moreover, the mechanisms by which different functional states within the cytokine-induced microglial state transition regulate AD pathology remain unclear. In this review, we summarize how different cytokine signaling pathways, including those of IL-33 (interleukin-33), NLRP3 inflammasome–IL-1β, IL-10, and IL-12/IL-23, regulate microglial functions in AD. Furthermore, we discuss how the modulation of these cytokine signaling pathways can result in beneficial outcomes in AD. Finally, we describe a stepwise functional state transition of microglia induced by cytokine signaling that can provide insights into the molecular basis of the beneficial effects of cytokine modulation in AD and potentially aid therapeutic development.

scholarly journals Methamphetamine and Modulation Functionality of the Prelimbic Cortex for Developing a Possible Treatment of Alzheimer’s Disease in an Animal Model

2021 ◽  
Vol 13 ◽  
Author(s):  
Bai-Chuang Shyu ◽  
Zhi-Yue Gao ◽  
José Jiun-Shian Wu ◽  
Alan Bo Han He ◽  
Cai-N Cheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Cognitive Function ◽  
Neural Activity ◽  
Neural Plasticity ◽  
Plasma Corticosterone ◽  
Prelimbic Cortex ◽  
Saccharin Intake ◽  
Fos Expression

Alzheimer’s disease (AD) is a progressive neurodegenerative condition that causes cognitive impairment and other neuropsychiatric symptoms. Previously, little research has thus far investigated whether methamphetamine (MAMPH) can enhance cognitive function or ameliorate AD symptoms. This study examined whether a low dose of MAMPH can induce conditioned taste aversion (CTA) learning, or can increase plasma corticosterone levels, neural activity, and neural plasticity in the medial prefrontal cortex (mPFC) (responsible for cognitive function), the nucleus accumbens (NAc) and the amygdala (related to rewarding and aversive emotion), and the hippocampus (responsible for spatial learning). Furthermore, the excitations or lesions of the prelimbic cortex (PrL) can affect MAMPH-induced CTA learning, plasma corticosterone levels, and neural activity or plasticity in the mPFC [i.e., PrL, infralimbic cortex (IL), cingulate cortex 1 (Cg1)], the NAc, the amygdala [i.e., basolateral amygdala (BLA) and central amygdala (CeA)], and the hippocampus [i.e., CA1, CA2, CA3, and dentate gyrus (DG)]. In the experimental procedure, the rats were administered either saline or NMDA solutions, which were injected into the PrL to excite or destroy PrL neurons. Additionally, rats received 0.1% saccharin solution for 15 min, followed by intraperitoneal injections of either normal saline or 1 mg/kg MAMPH to induce CTA. A one-way ANOVA was performed to analyze the effects of saccharin intake on CTA, plasma corticosterone levels, and the expression of c-Fos and p-ERK. The results showed that the MAMPH induced CTA learning and increased plasma corticosterone levels. The mPFC, and particularly the PrL and IL and the DG of the hippocampus, appeared to show increased neural activity in c-Fos expression or neural plasticity in p-ERK expression. The excitation of the PrL neurons upregulated neural activity in c-Fos expression and neural plasticity in p-ERK expression in the PrL and IL. In summary, MAMPH may be able to improve cognitive and executive function in the brain and reduce AD symptoms. Moreover, the excitatory modulation of the PrL with MAMPH administration can facilitate MAMPH-induced neural activity and plasticity in the PrL and IL of the mPFC. The present data provide clinical implications for developing a possible treatment for AD in an animal model.

scholarly journals Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer’s Disease: Compensation and Dysfunction

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhen Zhang ◽  
Liang Cui ◽  
Yanlu Huang ◽  
Yu Chen ◽  
Yuehua Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Frontal Lobe ◽  
Temporal Lobe ◽  
Neural Activity ◽  
Neuropsychological Tests ◽  
Parietal Lobe ◽  
Neuropsychological Test ◽  
Potential Biomarker

IntroductionSubjective cognitive decline (SCD) is the preclinical stage of Alzheimer’s disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients.Materials and Methods37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed.ResultsOur results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group’s neuropsychological test performance was significantly lower than that of the SCD group.ConclusionThere are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group’s cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.

scholarly journals IL-33-PU.1 Transcriptome Reprogramming Drives Functional State Transition and Clearance Activity of Microglia in Alzheimer’s Disease

Cell Reports ◽  
2020 ◽  
Vol 31 (3) ◽  
pp. 107530
Author(s):  
Shun-Fat Lau ◽  
Congping Chen ◽  
Wing-Yu Fu ◽  
Jianan Y. Qu ◽  
Tom H. Cheung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional State ◽  
State Transition

Characterization of the dynamic behavior of neural activity in Alzheimer’s disease: exploring the non-stationarity and recurrence structure of EEG resting-state activity

2020 ◽  
Vol 17 (1) ◽  
pp. 016071 ◽  
Author(s):  
Pablo Núñez ◽  
Jesús Poza ◽  
Carlos Gómez ◽  
Verónica Barroso-García ◽  
Aarón Maturana-Candelas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dynamic Behavior ◽  
Neural Activity ◽  
Resting State ◽  
State Activity

scholarly journals Assessment of Neurovascular Coupling & Cortical Spreading Depression in Mixed Models of Atherosclerosis & Alzheimer’s Disease

2020 ◽  
Author(s):  
Osman Shabir ◽  
Ben Pendry ◽  
Llywelyn Lee ◽  
Beth Eyre ◽  
Paul Sharp ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neural Activity ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Neurovascular Coupling ◽  
Disease Models ◽  
Brain State ◽  
The Brain ◽  
Dementia Onset

AbstractNeurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. However, experimental data commonly arise from preclinical models in young mice with one disease only. In this study, we examined cortical haemodynamics in preparations that modelled common co-existing conditions namely Alzheimer’s disease (J20-AD) combined with atherosclerosis (PCSK9-ATH) between 9-12m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume (HbT), levels of oxyhaemoglobin (HbO) & deoxyhaemoglobin (HbR), in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a highly significant increase (3x fold) in hippocampal amyloid-beta plaques, without any further alterations to neurovascular function. There were no significant changes in evoked neural activity in any of the disease models, suggesting a breakdown of neurovascular coupling in PCSK9-ATH mice with inadequate oxygen delivery. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia and potentially ischaemia. The inflammatory environment in the brain was also perturbed, with interleukin-1 beta raised up to 2-fold and tumour necrosis factor raised up to 7-fold in brain tissues from these mice. Taken together, these findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.Significance StatementThe development of therapies for dementia is one of the biggest scientific priorities as many amyloid-targeting treatments have failed clinical trials in the past, and to date, we have no disease modifying therapies. Understanding the different disease mechanisms involved in the onset of dementia is important if therapies are to succeed. Evidence has pointed to vascular dysfunction as a key potential mechanism involved in dementia onset and many preclinical studies have highlighted the role of impaired neurovascular coupling in such models. In this study we report novel findings with respect to neurovascular dysfunction in disease models, as well as describing how brain state plays a role in worsened outcomes of brain injury and migraine in the context of dementia onset.

scholarly journals Quasi-Periodic Patterns of Neural Activity improve Classification of Alzheimer’s Disease in Mice

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Michaël E. Belloy ◽  
Disha Shah ◽  
Anzar Abbas ◽  
Amrit Kashyap ◽  
Steffen Roßner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neural Activity ◽  
Periodic Patterns

scholarly journals Author Correction: Quasi-Periodic Patterns of Neural Activity improve Classification of Alzheimer’s Disease in Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Michaël E. Belloy ◽  
Disha Shah ◽  
Anzar Abbas ◽  
Amrit Kashyap ◽  
Steffen Roßner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neural Activity ◽  
Periodic Patterns

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease

NeuroImage ◽  
2018 ◽  
Vol 169 ◽  
pp. 302-311 ◽  
Author(s):  
Giacomo Koch ◽  
Sonia Bonnì ◽  
Maria Concetta Pellicciari ◽  
Elias P. Casula ◽  
Matteo Mancini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcranial Magnetic Stimulation ◽  
Neural Activity ◽  
Magnetic Stimulation ◽  
Prodromal Alzheimer’S Disease ◽  
Stimulation Of
Sign in / Sign up

Export Citation Format

Share Document