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 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

Berberine Alleviates Amyloid-beta Pathogenesis Via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Zhi-You Cai ◽  
Chuan-Ling Wang ◽  
Tao-Tao Lu ◽  
Wen-Ming Yang
Keyword(s):  
Transgenic Mice ◽  
Western Blotting ◽  
Amyloid Β ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Enzyme Linked Immunosorbent Assay ◽  
Synaptic Density ◽  
Ampk Signaling ◽  
The Brain ◽  
Post Synaptic Density

Background:Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology.Methods:The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry.Results:BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice.Conclusion:BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 19 (3) ◽  
pp. 316-325
Author(s):  
Mahdi Goudarzvand ◽  
Yaser Panahi ◽  
Reza Yazdani ◽  
Hosein Miladi ◽  
Saeed Tahmasebi ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Mediators ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Gavage ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
17Β Estradiol ◽  
The Brain ◽  
Experimental Autoimmune

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

scholarly journals Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 621
Author(s):  
Ernest Adeghate ◽  
Crystal M. D’Souza ◽  
Zulqarnain Saeed ◽  
Saeeda Al Jaberi ◽  
Saeed Tariq ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kidney Tubules ◽  
Onset Of Diabetes ◽  
Endogenous Antioxidants ◽  
Kidney Liver ◽  
Convoluted Tubules ◽  
The Brain

Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.

scholarly journals The Modular Organization of Pain Brain Networks: An fMRI Graph Analysis Informed by Intracranial EEG

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Camille Fauchon ◽  
David Meunier ◽  
Isabelle Faillenot ◽  
Florence B Pomares ◽  
Hélène Bastuji ◽  
...  
Keyword(s):  
Information Integration ◽  
Functional Organization ◽  
Brain Connectivity ◽  
Brain Networks ◽  
Modular Organization ◽  
Noxious Heat ◽  
Intracranial Eeg ◽  
Brain Connectome ◽  
Posterior Parietal ◽  
The Brain

Abstract Intracranial EEG (iEEG) studies have suggested that the conscious perception of pain builds up from successive contributions of brain networks in less than 1 s. However, the functional organization of cortico-subcortical connections at the multisecond time scale, and its accordance with iEEG models, remains unknown. Here, we used graph theory with modular analysis of fMRI data from 60 healthy participants experiencing noxious heat stimuli, of whom 36 also received audio stimulation. Brain connectivity during pain was organized in four modules matching those identified through iEEG, namely: 1) sensorimotor (SM), 2) medial fronto-cingulo-parietal (default mode-like), 3) posterior parietal-latero-frontal (central executive-like), and 4) amygdalo-hippocampal (limbic). Intrinsic overlaps existed between the pain and audio conditions in high-order areas, but also pain-specific higher small-worldness and connectivity within the sensorimotor module. Neocortical modules were interrelated via “connector hubs” in dorsolateral frontal, posterior parietal, and anterior insular cortices, the antero-insular connector being most predominant during pain. These findings provide a mechanistic picture of the brain networks architecture and support fractal-like similarities between the micro-and macrotemporal dynamics associated with pain. The anterior insula appears to play an essential role in information integration, possibly by determining priorities for the processing of information and subsequent entrance into other points of the brain connectome.

scholarly journals Effects of Transcranial Ultrasound Stimulation on Trigeminal Blink Reflex Excitability

2021 ◽  
Vol 11 (5) ◽  
pp. 645
Author(s):  
Andrea Guerra ◽  
Edoardo Vicenzini ◽  
Ettore Cioffi ◽  
Donato Colella ◽  
Antonio Cannavacciuolo ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Blink Reflex ◽  
Transcranial Ultrasound ◽  
Recovery Cycle ◽  
Brain Areas ◽  
Nucleus Raphe Magnus ◽  
Ultrasound Stimulation ◽  
Raphe Magnus ◽  
Interstimulus Intervals

Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans. The recovery cycle of the trigeminal blink reflex (interstimulus intervals of 250 and 500 ms) was tested before (T0), and 3 (T1) and 30 min (T2) after TUS. The effects of substantia nigra-TUS, superior colliculus-TUS, nucleus raphe magnus-TUS and sham-TUS were assessed in separate and randomized sessions. In the superior colliculus-TUS session, the conditioned R2 area increased at T1 compared with T0, while T2 and T0 values did not differ. Results were independent of the interstimulus intervals tested and were not related to trigeminal blink reflex baseline (T0) excitability. Conversely, the conditioned R2 area was comparable at T0, T1, and T2 in the nucleus raphe magnus-TUS and substantia nigra-TUS sessions. Our findings demonstrate that the excitability of brainstem circuits, as evaluated by testing the recovery cycle of the trigeminal blink reflex, can be increased by TUS. This result may reflect the modulation of inhibitory interneurons within the superior colliculus.

scholarly journals Dezocine Prevents Postoperative Hyperalgesia in Patients Undergoing Open Abdominal Surgery

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Fang Yu ◽  
Jie Zhou ◽  
Suyun Xia ◽  
Huan Xu ◽  
Xiangrui Wang
Keyword(s):  
Treatment Group ◽  
Abdominal Surgery ◽  
Pain Threshold ◽  
Controlled Trial ◽  
Thermal Hyperalgesia ◽  
Postoperative Nausea And Vomiting ◽  
Open Gastrectomy ◽  
Sham Treatment ◽  
Pain Scores ◽  
Open Abdominal Surgery

Objective. Postoperative hyperalgesia is very frequent and hard to treat. Dezocine is widely used and has a modulatory effect for thermal hyperalgesia in animal models. So, this study was designed to investigate the potential role of dezocine in decreasing postoperative hyperalgesia for patients undergoing open abdominal surgery.Methods. This is a randomized, double-blinded, and placebo-controlled trial. 50 patients for elective open gastrectomy were randomly allocated to either a true treatment group (0.15 mg/kg intravenous dezocine at the end of surgery) or a sham treatment group (equivalent volume of saline) in a 1 : 1 ratio. Patients were followed up for 48 hours postoperatively and pain threshold to Von Frey filaments, pain scores, PCIA consumption, rescue analgesics use, sedation score, and occurrence of postoperative nausea and vomiting were recorded.Results. Patients in the true treatment group experienced statistically significantly higher pain threshold on forearm and smaller extent of peri-incisional hyperalgesia than the sham treatment group. Rescue analgesic use, cumulative PCIA consumption, and pain scores were statistically significantly decreased in the true treatment group compared to the sham treatment group.Conclusions. Dezocine offers a significant antihyperalgesic and analgesic effect in patients undergoing elective open gastrectomy for up to 48 hours postoperatively.

scholarly journals The Brain Connectivity Basis of Semantic Dementia: A Selective Review

2015 ◽  
Vol 21 (10) ◽  
pp. 784-792 ◽  
Author(s):  
Qing Yang ◽  
Qi-Hao Guo ◽  
Yan-Chao Bi
Keyword(s):  
Brain Connectivity ◽  
Semantic Dementia ◽  
Selective Review ◽  
The Brain
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