scholarly journals Effects of Transcranial Ultrasound Stimulation Pulsed at 40 Hz on Aβ Plaques and Brain Rhythms in 5XFAD Mice

2021 ◽  
Author(s):  
Mincheol Park ◽  
Gia Minh Hoang ◽  
Thien Nguyen ◽  
Eunkyung Lee ◽  
Hyun Jin Jung ◽  
...  
Keyword(s):  
Treatment Group ◽  
Mouse Model ◽  
Brain Connectivity ◽  
Transcranial Ultrasound ◽  
Sham Treatment ◽  
Ultrasound Stimulation ◽  
Gamma Power ◽  
5Xfad Mice ◽  
The Brain ◽  
Ad Mouse Model

Abstract BackgroundAlzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological treatments. The impairment in the gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently the therapeutic effect of gamma entrainment treatment on the AD mouse model was reported. Given that ultrasound is an emerging modality of neuromodulation, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40Hz) on an AD mouse model. MethodsWe implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-months-old 5XFAD and wild-type control mice (n=12 and 6, respectively). Six 5XFAD mice were treated with daily two-hour ultrasound stimulation at 40Hz for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. ResultsWe found that total Aβ 42 and 40 levels, especially insoluble, in the treatment group decreased compared to that of the sham treatment group. The reduction in the number of Aβ plaques in PIL also has been shown. In addition, spontaneous gamma power was increased, and brain connectivity was improved. ConclusionsThese results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity

scholarly journals Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Mincheol Park ◽  
Gia Minh Hoang ◽  
Thien Nguyen ◽  
Eunkyung Lee ◽  
Hyun Jin Jung ◽  
...  
Keyword(s):  
Treatment Group ◽  
Brain Connectivity ◽  
Transcranial Ultrasound ◽  
Enzyme Linked Immunosorbent Assay ◽  
Limbic Cortex ◽  
Sham Treatment ◽  
Ultrasound Stimulation ◽  
Gamma Power ◽  
The Brain ◽  
40 Hz

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently, the therapeutic effect of gamma entrainment in AD mouse models has been reported. Given that ultrasound is an emerging neuromodulation modality, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40 Hz) in an AD mouse model. Methods We implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice (n = 12 and 6, respectively). Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. Results We found that the total Aβ42 levels, especially insoluble Aβ42, in the treatment group decreased in pre- and infra-limbic cortex (PIL) compared to that of the sham treatment group. A reduction in the number of Aβ plaques was also observed in the hippocampus. There was no increase in microbleeding in the transcranial ultrasound stimulation (tUS) group. In addition, the length and number of microglial processes decreased in PIL and hippocampus. Encelphalographic spontaneous gamma power was increased, and cross-frequency coupling was normalized, implying functional improvement after tUS stimulation. Conclusion These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity.

scholarly journals A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
William J. Behof ◽  
Clayton A. Whitmore ◽  
Justin R. Haynes ◽  
Adam J. Rosenberg ◽  
Mohammed N. Tantawy ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mouse Model ◽  
Peripheral Tissues ◽  
Molar Activity ◽  
Model Of Alzheimer’S Disease ◽  
Specific Retention ◽  
5Xfad Mice ◽  
The Brain

AbstractErgothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.

scholarly journals Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 144 ◽  
Author(s):  
A. Erramuzpe ◽  
J. M. Encinas ◽  
A. Sierra ◽  
M. Maletic-Savatic ◽  
A.L. Brewster ◽  
...  
Keyword(s):  
Case Report ◽  
Status Epilepticus ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Latent Period ◽  
Brain Connectivity ◽  
Low Frequency ◽  
Longitudinal Variations ◽  
Brain Functional Connectivity ◽  
The Brain

Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain.FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry.Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC across three stages:  1, the initial insult (status epilepticus); 2, the latent period, when epileptogenic networks emerge; and 3, chronic epilepsy, when unprovoked seizures occur as spontaneous events.We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity  of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

scholarly journals A Derivative of the Brain Metabolite Lanthionine Ketimine Improves Cognition and Diminishes Pathology in the 3×Tg-AD Mouse Model of Alzheimer Disease

2013 ◽  
Vol 72 (10) ◽  
pp. 955-969 ◽  
Author(s):  
Kenneth Hensley ◽  
S. Prasad Gabbita ◽  
Kalina Venkova ◽  
Alexandar Hristov ◽  
Ming F. Johnson ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Mouse Model ◽  
Brain Metabolite ◽  
The Brain ◽  
Ad Mouse Model

Neoline Improves Memory Impairment and Reduces Amyloid-β Level and Tau Phosphorylation Through AMPK Activation in the Mouse Alzheimer’s Disease Model

2021 ◽  
pp. 1-10
Author(s):  
Quan Feng Liu ◽  
Suganya Kanmani ◽  
Jinhyuk Lee ◽  
Geun-Woo Kim ◽  
Songhee Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Chronic Administration ◽  
Therapeutic Effects ◽  
Ampk Activation ◽  
The Brain ◽  
Ad Mouse Model

Background: Alzheimer’s disease (AD) is the most general, chronic, and progressive neurodegenerative senile disorder characterized clinically by progressive cognitive deterioration and memory impairment. Neoline is effective against neuropathic pain models, but the effects of neoline against AD-like phenotypes have not been investigated. Objective: We offer the investigation of the effects of neoline in AD. Methods: In this study, a Tg-APPswe/PS1dE9 AD mouse model was treated orally with neoline at a concentration of 0.5 mg/kg or 0.1 mg/kg starting at 7.5 months and administered for three months, and its anti-AD effects were evaluated. Results: Neoline improved memory and cognition impairments and reduced the number of amyloid-beta plaque and the amount of amyloid-β in the brain of AD mice. Furthermore, neoline reduced the anxiety behavior in the AD mouse model. The chronic administration of neoline also induced AMPK phosphorylation and decreased tau, amyloid-β, and BACE1 expression in the hippocampus. These findings indicate that chronic administration of neoline has therapeutic effects via AMPK activation, and BACE1 downregulation resulted in a decrease in the amyloid-β levels in the brain of Tg-APPswe/PS1dE9 AD mice. Conclusion: Our results suggest that neoline is a therapeutic agent for the cure of neurodegenerative diseases like AD.

scholarly journals Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 144
Author(s):  
A. Erramuzpe ◽  
J. M. Encinas ◽  
A. Sierra ◽  
M. Maletic-Savatic ◽  
A.L. Brewster ◽  
...  
Keyword(s):  
Case Report ◽  
Status Epilepticus ◽  
Functional Connectivity ◽  
Mouse Model ◽  
Latent Period ◽  
Brain Connectivity ◽  
Low Frequency ◽  
Longitudinal Variations ◽  
Brain Functional Connectivity ◽  
The Brain

Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC changes from the initial insult (status epilepticus) and over the latent period, when epileptogenic networks emerge, and at chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

scholarly journals Spatial memory deficiency early in 6xTg Alzheimer’s disease mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinwoo Kang ◽  
Jinho Kim ◽  
Keun-A Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Spatial Memory ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Cognitive Changes ◽  
Synaptic Loss ◽  
5Xfad Mice ◽  
Ad Mouse Model

AbstractAlzheimer’s disease (AD) is mainly characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFTs). While the recent 5xFAD AD mouse model exhibits many AD-related phenotypes and a relatively early and aggressive amyloid β production, it does not show NFTs. Here, we developed and evaluated a novel AD mouse model (6xTg-AD, 6xTg) by crossbreeding 5xFAD mice with mice expressing mutant (P301L) tau protein (MAPT). Through behavioral and histopathological tests, we analyzed cognitive changes and neuropathology in 6xTg mice compared to their respective parental strains according to age. Spatial memory deficits occurred in 6xTg mice at 2 months of age, earlier than they occurred in 5xFAD mice. Histopathological data revealed aggressive Aβ42 and p-tau accumulation in 6xTg mice. Microglial activation occurred in the cortex and hippocampus of 6xTg mice beginning at 2 months. In 6xTg model mice, the synaptic loss was observed in the cortex from 4 months of age and in the hippocampus from 6 months of age, and neuronal loss appeared in the cortex from 4 months of age and in the hippocampus 6 months of age, earlier than it is observed in the 5xFAD and JNPL3 models. These results showed that each pathological symptom appeared much faster than in their parental animal models. In conclusion, these novel 6xTg-AD mice might be an advanced animal model for studying AD, representing a promising approach to developing effective therapy.

scholarly journals Changes in the brain transcriptome after DNA Aβ42 trimer immunization in a 3xTg-AD mouse model

2021 ◽  
Vol 148 ◽  
pp. 105221
Author(s):  
Doris Lambracht-Washington ◽  
Min Fu ◽  
Linda S. Hynan ◽  
Roger N. Rosenberg
Keyword(s):  
Mouse Model ◽  
Brain Transcriptome ◽  
The Brain ◽  
Ad Mouse Model
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