scholarly journals Neuromodulation of the cerebellum rescues movement in a mouse model of ataxia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lauren N. Miterko ◽  
Tao Lin ◽  
Joy Zhou ◽  
Meike E. van der Heijden ◽  
Jaclyn Beckinghausen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Early Stage ◽  
Low Frequency ◽  
Cerebellar Nuclei ◽  
Motor Dysfunction ◽  
Motor Center ◽  
Limb Coordination ◽  
Potential Benefits ◽  
Circuit Function ◽  
The Brain

AbstractDeep brain stimulation (DBS) relieves motor dysfunction in Parkinson’s disease, and other movement disorders. Here, we demonstrate the potential benefits of DBS in a model of ataxia by targeting the cerebellum, a major motor center in the brain. We use the Car8 mouse model of hereditary ataxia to test the potential of using cerebellar nuclei DBS plus physical activity to restore movement. While low-frequency cerebellar DBS alone improves Car8 mobility and muscle function, adding skilled exercise to the treatment regimen additionally rescues limb coordination and stepping. Importantly, the gains persist in the absence of further stimulation. Because DBS promotes the most dramatic improvements in mice with early-stage ataxia, we postulated that cerebellar circuit function affects stimulation efficacy. Indeed, genetically eliminating Purkinje cell neurotransmission blocked the ability of DBS to reduce ataxia. These findings may be valuable in devising future DBS strategies.

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

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 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 The Anti-Diabetic Drug Metformin Rescues Aberrant Mitochondrial Activity and Restrains Oxidative Stress in a Female Mouse Model of Rett Syndrome

2020 ◽  
Vol 9 (6) ◽  
pp. 1669 ◽  
Author(s):  
Ilaria Zuliani ◽  
Chiara Urbinati ◽  
Daniela Valenti ◽  
Maria Cristina Quattrini ◽  
Vanessa Medici ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Rett Syndrome ◽  
Systemic Treatment ◽  
Drug Repurposing ◽  
Motor Dysfunction ◽  
Mitochondrial Activity ◽  
Atp Production ◽  
First Line Therapy ◽  
The Brain

Metformin is the first-line therapy for diabetes, even in children, and a promising attractive candidate for drug repurposing. Mitochondria are emerging as crucial targets of metformin action both in the periphery and in the brain. The present study evaluated whether treatment with metformin may rescue brain mitochondrial alterations and contrast the increased oxidative stress in a validated mouse model of Rett syndrome (RTT), a rare neurologic disorder of monogenic origin characterized by severe behavioral and physiological symptoms. No cure for RTT is available. In fully symptomatic RTT mice (12 months old MeCP2-308 heterozygous female mice), systemic treatment with metformin (100 mg/kg ip for 10 days) normalized the reduced mitochondrial ATP production and ATP levels in the whole-brain, reduced brain oxidative damage, and rescued the increased production of reactive oxidizing species in blood. A 10-day long treatment with metformin also boosted pathways related to mitochondrial biogenesis and antioxidant defense in the brain of metformin-treated RTT mice. This treatment regimen did not improve general health status and motor dysfunction in RTT mice at an advanced stage of the disease. Present results provide evidence that systemic treatment with metformin may represent a novel, repurposable therapeutic strategy for RTT.

scholarly journals Host Immune Response to ZIKV in an Immunocompetent Embryonic Mouse Model of Intravaginal Infection

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 558 ◽  
Author(s):  
Svetlana F. Khaiboullina ◽  
Priscila Lopes ◽  
Toniana G. de Carvalho ◽  
Ana Luiza C. V. Real ◽  
Danielle G. Souza ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Early Stage ◽  
Host Immune Response ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Embryonic Mouse ◽  
Human Pathology ◽  
Congenital Zika Syndrome ◽  
The Brain

Zika virus (ZIKV) only induces mild symptoms in adults; however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of the host immune response to ZIKV becomes challenging in these animals. Thus, the main goal of this study was to develop an immunocompetent mouse model to study the ZIKV spread and teratogeny. FVB/NJ immune competent dams were infected intravaginally with ZIKV during the early stage of pregnancy. We found that the placentae of most fetuses were positive for ZIKV, while the virus was detected in the brain of only about 42% of the embryos. To investigate the host immune response, we measured the expression of several inflammatory factors. Embryos from ZIKV-infected dams had an increased level of inflammatory factors, as compared to Mock. Next, we compared the gene expression levels in embryos from ZIKV-infected dams that were either negative or positive for ZIKV in the brain. The mRNA levels of viral response genes and cytokines were increased in both ZIKV-positive and negative brains. Interestingly, the levels of chemokines associated with microcephaly in humans, including CCL2 and CXCL10, specifically increased in embryos harboring ZIKV in the embryo brains.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

Changes in the Total Power of Beta and Theta Bands When Using EEG Biofeedback in Primary School-Age Children Having Difficulties with Voluntary Regulation

2020 ◽  
pp. 331-340
Author(s):  
Yuliya S. Dzhos ◽  
◽  
Irina A. Men’shikova ◽  
Keyword(s):  
Left Hemisphere ◽  
Spectral Characteristics ◽  
Low Frequency ◽  
School Age Children ◽  
Total Power ◽  
Eeg Biofeedback ◽  
Beta Band ◽  
Bioelectric Activity ◽  
Voluntary Regulation ◽  
The Brain

This article presents the results of the study on spectral electroencephalogram (EEG) characteristics in 7–10-year-old children (8 girls and 22 boys) having difficulties with voluntary regulation of activity after 10 and 20 neurofeedback sessions using beta-activating training. Brain bioelectric activity was recorded in 16 standard leads using the Neuron-Spectrum-4/VPM complex. The dynamics was assessed by EEG beta and theta bands during neurofeedback. An increase in the total power of beta band oscillations was established both after 10 and after 20 sessions of EEG biofeedback in the frontal (p ≤ 0.001), left parietal (p ≤ 0.036), and temporal (p ≤ 0.003) areas of the brain. A decrease in the spectral characteristics of theta band oscillations was detected: after 10 neurofeedback sessions in the frontal (p ≤ 0.008) and temporal (p ≤ 0.006) areas of both hemispheres, as well as in the parietal area of the left hemisphere (p ≤ 0.005); after 20 sessions, in the central (p ≤ 0.004), frontal (p ≤ 0.001) and temporal (p ≤ 0.001) areas of both hemispheres, as well as in the occipital (p ≤ 0.047) and parietal (p ≤ 0.001) areas of the left hemisphere. The study into the dynamics of bioelectric activity during biofeedback using EEG parameters in 7–10-year-old children with impaired voluntary regulation of higher mental functions allowed us to prove the advisability of 20 sessions, as the increase in high-frequency activity and decrease in low-frequency activity do not stop with the 10th session. Changes in these parameters after 10 EEG biofeedback sessions are expressed mainly in the frontotemporal areas of both hemispheres, while after a course of 20 sessions, in both the frontotemporal and central parietal areas of the brain.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

2020 ◽  
Vol 13 ◽  
Author(s):  
Shoaib Amin Banday ◽  
Mohammad Khalid Pandit
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Sagittal Plane ◽  
Early Stage ◽  
Imaging Techniques ◽  
Complex Structure ◽  
Magnetic Resonance Images ◽  
Absolute Difference ◽  
Brain Hemispheres ◽  
The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

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