Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
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Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by loss of neurons and synaptic transmission interruption, eventually causing cognitive deficits. At the beginning of the disease, the olfactory pathways appear to be most sensitive to tauopathy, while most studies have focused on the plasticity of hippocampal circuits.
Functional network connectivity (FC) and long-term potentiation (LTP), regarded as the substrate plasticity of learning and memory, which is longitudinally assessed on a rat model of P301S of tauopathy follow courses (time and location) pathology of progressive neurodegenerative (ie, at 3, 6, and 9 months of age) and their wild-type (WT) littermates. Using in vivo potency local field (LFP) recordings, beginning (at three months) absorbers in activity oscillates gamma and interference in the coupling phase-amplitude theta-gamma (PAC) found in the olfactory bulb (OB) circuitry P301S mice, which was maintained through the entire program of development of pathology. In contrast, activity LFP oscillations and normal PAC index in the entorhinal cortex, hippocampal CA1 and CA3 core.
Field excitatory postsynaptic potential (fEPSP) recording of collateral Shaffer (SC) -CA1 hippocampal LTP strata of the pyramid reveals significantly altered synaptic responses against high frequency stimulation (HFS): at three months of age, there was no significant difference between the genotype was found in the basal synaptic activity , while signs of short-term plasticity deficits revealed by changes in fEPSPs. At the age of six months, a little deviation found in the basal synaptic activity and significant differences were observed in response to the LTP. The change in network oscillations in the level of OB and disruption in the functioning of the SC-CA1 synapses pyramid strongly suggest that the development of tau pathology causing brain areas, disruption of activity-dependent synaptic transmission functional.
These findings indicate a major change early activity of neurons in the OB circuit before hippocampal synaptic plasticity disorders, may involve tauopathy in anomaly FC. Further studies should determine whether they are deficits in the early oscillation OB and FC network is a mechanism that may potentially promote the emergence of hippocampal synaptic disruption during development tauopathy.
Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
Use of Biomarkers in ongoing Alzheimer’s Disease Research Protocols
This study aims to describe and discuss the state of the art the use of biomarkers in the ongoing study of disease (AD) Alzheimer’s. A review of 222 ongoing phase 1, 2, 3, and 4 protocols listed in the database clinicaltrials.gov do. All trials (i) subjects enrolled in a clinical disorder and / or diagnosis of preclinical included in the continuum of AD; and (ii) to test the efficacy and / or safety / tolerability of the therapeutic intervention, were analyzed.
The use of biomarkers of amyloid deposition, tau pathology and neurodegeneration among the eligibility criteria and / or the results of the study assessed. Overall, 58.2% of the intervention study was underway on adopting AD biomarker candidates. They largely adopted by studies in the early stages of the drug development process to explore the safety profile of new therapies, and to provide evidence of target engagement and disease-modifying properties.
Total Protein - Alzheimer's Disease: Brain: Hippocampus
Description: Human hippocamps tissue lysate was prepared by homogenization using a proprietary technique. The tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The human hippocamps tissue total protein is provided in a buffer including HEPES (pH7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, Sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the hippocamps tissue pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The hippocamps tissue is then Western analyzed by either GAPDH or β-actin antibody, and the expression level is consistent with each lot.
Tissue cDNA, First Strand, Human Diseased, Alzheimer's Disease, Brain, Hippocampus, BioGenomics
Description: Human brain hippocamps tissue cytoplasmic protein lysate was prepared by isolating the cytoplasmic protein from whole tissue homogenates using a proprietary technique. The human hippocamps tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The cytoplasmic protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, glycerol, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain hippocamps tissue cytoplasmic protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain hippocamps tissue cytoplasmic protein is then Western analyzed by GAPDH antibody, and the expression level is consistent with each lot.
Membrane Protein - Alzheimer's Disease:Brain: Amygdala
Description: Human brain amygdala tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human amygdala tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain amygdala tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain amygdala tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human brain temporal lobe tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human temporal lobe tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain temporal lobe tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain temporal lobe tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Description: Human brain hippocamps tissue membrane protein lysate was prepared by isolating the membrane protein from whole tissue homogenates using a proprietary technique. The human hippocamps tissue was frozen in liquid nitrogen immediately after excision and then stored at -70°C. The membrane protein is provided in a buffer including HEPES (pH 7.9), MgCl2, KCl, EDTA, Sucrose, Glycerol, sodium deoxycholate, NP-40, and a cocktail of protease inhibitors. For quality control purposes, the isolated brain hippocamps tissue membrane protein pattern on SDS-PAGE gel is shown to be consistent for each lot by visualization with coomassie blue staining. The isolated brain hippocamps tissue membrane protein is then Western analyzed by either GAPDH or β-actin antibody to confirm there is no signal or very weak signal.
Total Protein - Alzheimer's Disease: Brain: Frontal Lobe
Selection of participants supported biologically based largely on biomarkers of amyloid deposition, while the use of a biomarker as a result of the study largely depends on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. However, their clinical validity, utility, and cost-effectiveness in the “real world” remains to be clarified.
