Cerebellar Regions Research Articles

Associations between cerebellum and major psychiatric disorders: a bidirectional Mendelian randomization study.

Despite its small size the cerebellum is an anatomically complex and functionally important part of the brain. Previous studies have demonstrated associations between characteristic features/anatomic anomalies of cerebellum and psychiatric disorders. However, the potential causal relationships are unknown. In this study, a bidirectional two-sample Mendelian randomization approach was employed to investigate single nucleotide polymorphism (SNP) heritability and genetic causal associations between 77 imaging derived phenotypes (IDPs) of the cerebellum and major psychiatric disorder, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ) and attention deficit hyperactivity disorder (ADHD). We identified thirty IDPs for which there was evidence of a causal effect on risk of MDD, BD, SCZ and ADHD. For example, 1s.d. increase in the mean diffusivity (MD) of the left superior cerebellar peduncle was associated with 32% lower odds of BD risk. Reverse MR indicated that psychiatric disorders was associated with fourteen IDPs. For example, MDD were causally associated with three IDPs of gray matter volume (GMV) of right and left X cerebellum, and vermis crus II cerebellum. These results suggested that there were genetic causal associations between psychiatric disorders and certain cerebellum regions, such as the cognitive function of posterior cerebellar lobes and the connection of cerebellar to cerebrum. Further investigations need to enhance prediction and intervention strategies for potential psychiatric disorder risks.

Brainstem and cerebellar radiological findings in progressive supranuclear palsy

Abstract Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative 4-repeat (4R) tauopathy associated with significant morbidity. Heterogeneity of symptom expression among this group is increasingly recognized, reflecting variable tau spread and neurodegeneration. Clinical manifestations consist of debilitating and rapidly progressive motor, oculomotor, speech, cognitive and affective impairments. Core pathological changes are noted with a predominance in the midbrain and basal ganglia, however spread to the more caudal brainstem and cerebellar regions is reported at various stages. Accordingly, whilst midbrain atrophy is the best recognized supportive imaging finding, quantitative neuroimaging studies using MRI and PET approaches have revealed a wider profile of brain abnormalities in cohorts of individuals with PSP. This expanded neurobiological scope of disease may account for individual heterogeneity and may highlight additional biological markers that are relevant to diagnosing and tracking the illness. Additionally, there is increasing understanding of the diverse cognitive, affective and speech functions of the cerebellum, which may be implicated in PSP beyond current recognition. In this review, we undertake a systematic literature search and summary of in vivo structural and functional neuroimaging findings in the brainstem and cerebellum in PSP to date. Novel and multimodal imaging techniques have emerged over recent years, which reveal several infratentorial alterations beyond midbrain atrophy in PSP. Most saliently, there is evidence for volume loss and microstructural damage in the pons, middle cerebellar peduncles and cerebellar cortex and deep nuclei, reported alongside recognised midbrain and superior cerebellar peduncle changes. Whilst the literature supporting the presence of these features is not unanimous, the evidence base is compelling, including correlations with disease progression, severity, or variant differences. A smaller number of studies report on abnormalities in MRI measures of iron deposition, neuromelanin, viscoelasticity, and the glymphatic system involving the infratentorial regions. Molecular imaging studies have also shown increased uptake of tau tracer in the midbrain and cerebellar dentate nucleus, although concern remains regarding possible off-target binding. Imaging of other molecular targets has been sparse, but reports of neurotransmitter, inflammatory and synaptic density alterations in cerebellar and brainstem regions are available. Taken together, there is an established evidence base of in vivo imaging alterations in the brainstem and cerebellum which highlight that midbrain atrophy is often accompanied by other infratentorial alterations in people with PSP. Further research examining the contribution of these features to clinical morbidity and inter-individual variability in symptom expression is warranted.

Cerebellar-hippocampal volume associations with behavioral outcomes following tDCS modulation.

Here, we explore the relationship between transcranial direct current stimulation (tDCS) and brain-behavior interactions. We propose that tDCS perturbation allows for the investigation of relationships between brain volume and behavior. We focused on the hippocampus (HPC) and cerebellum (CB) regions that are implicated in our understanding of memory and motor skill acquisition. Seventy-four young adults (mean age: 22 ± 0.42 years, mean education: 14.7 ± 0.25 years) were randomly assigned to receive either anodal, cathodal, or sham stimulation. Following stimulation, participants completed computerized tasks assessing working memory and sequence learning in a magnetic resonance imaging (MRI) environment. We investigated the statistical interaction between CB and HPC volumes. Our findings showed that individuals with larger cerebellar volumes had shorter reaction times (RT) on a high-load working memory task in the sham stimulation group. In contrast, the anodal stimulation group exhibited faster RTs during the low-load working memory condition. These RT differences were associated with the cortical volumetric interaction between CB-HPC. Literature suggests that anodal stimulation down-regulates the CB and here, those with larger volumes perform more quickly, suggesting the potential need for additional cognitive resources to compensate for cerebellar downregulation or perturbation. This new insight suggests that tDCS can aid in revealing structure-function relationships, due to greater performance variability, especially in young adults. It may also reveal new targets of interest in the study of aging or in diseases where there is also greater behavioral variability.

Deviant sound frequency and time stimuli in auditory oddball tasks reveal persistent aberrant brain activity in patients with psychosis and symptomatic remission.

The detection of rare or deviant stimuli shares common brain circuits involved in temporal processing and salience, critical for cognitive control. Disruption in these processes may contribute to the mechanisms of the disease and explain cognitive deficits observed in psychosis and related disorders. We designed a neuroimaging study, using oddball task-based functional sequences (fMRI) and diffusion tensor imaging (DTI), comparing healthy controls (HC, n=14, 7 females) and patients with stable psychosis (PSY, n=20, 10 females). The PSY individuals had schizophrenia or bipolar disorder diagnosis (ICD-10), meeting symptom remission criteria in the last 6 months. Two variants of the auditory oddball paradigm were employed, focusing on sound frequency (SF) and time discrimination (TD) tasks, adapted for fMRI. We used a general linear model to analyze fMRI data and a random effects model for group analysis, complemented by an exploratory statistical agnostic mapping analysis. DTI data were processed using FSL (FMRIB Software Library) and TBSS (Tract Based Spatial Statistics). Distinct activation patterns between groups were observed, with increased brain activity in PSY in TD and SF oddball tasks. In response to increased task difficulty, HC predominantly activated cerebellar regions, whereas PSY relied more on frontal regions. Reduced fractional anisotropy in PSY correlated with lower performance scores in the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB). The study underscores aberrant brain activity and white matter deficits in stable psychosis patients, highlighting distinct responses to cognitive challenges compared to HC. These findings may support the hypothesis of cognitive dysmetria as a potential underlying mechanism in psychosis and highlight future therapeutic strategies, including non-invasive brain stimulation techniques.

Effects of trace element dysregulation on brain structure and function in spinocerebellar Ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder caused by excess CAG repeats in the ATXN3 gene, leads to progressive cerebellar ataxia and other symptoms. The results of previous studies suggest that trace element dysregulation contributes to neurodegenerative disorder onset. Here, we investigated the relationships of trace element dysregulation with CAG repeat length, clinical severity, and brain structural and functional connectivity in 45 patients with SCA3 and 44 healthy controls (HCs). Blood levels of lithium (Li), selenium (Se), and copper (Cu) were significantly lower in patients with SCA3 than in HCs; Li and Se levels were negatively correlated with CAG repeat length, especially in the manifest subgroup. Diffusion tensor imaging combined with resting-state functional magnetic resonance imaging revealed that Li levels were negatively correlated with fractional anisotropy in the white matter (WM) of bilateral frontal and parietal regions; tractography mapping showed disorder structural connectivity of Li-associated region nerve fiber pathways in patients with SCA3. Dynamic causal modeling analyses showed bidirectional causal connectivity from the inferior parietal lobule(IPL) to the cerebellum was significantly correlated with the blood level of Li in patients with SCA3. Time series correlation-based functional connectivity analysis revealed that the intrinsic connectivities of the bilateral dorsal premotor cortex(PMd) and IPL with local cerebellar regions were significantly weaker in patients with SCA3 than in HCs. Our results suggest that trace element dysregulation, especially Li deficiency, induces brain alterations and clinical manifestations in patients with SCA3; Li supplementation may be beneficial for WM or astrocytes in this patient population.

Cerebellum abnormalities in vascular mild cognitive impairment with depression symptom patients: A multimodal magnetic resonance imaging study.

Subcortical vascular mild cognitive impairment (svMCI) frequently occurs alongside depression symptoms, significantly affecting patients' quality of life. While cognitive decline and depression symptoms are linked to cerebellar changes, the specific relationship between these changes and cognitive status in svMCI patients with depression symptoms remains unclear. This study aimed to investigates the gray matter volume and functional alterations in the cerebellum of svMCI patients, with and without depression symptoms, and their correlation with cognitive and depressive symptoms. We enrolled 16 svMCI patients with depression symptoms (svMCI+D), 15 without (svMCI-D), and 12 normal controls (NC). Multimodal MRI scans were conducted, assessing gray matter volume and resting-state functional connectivity (RSFC) in the cerebellum. Correlations between RSFC and clinical scores from the Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD) were analyzed. Structural analysis indicated gray matter atrophy in left cerebellar lobules I_IV and VI (Cere6.L) in svMCI patients. svMCI+D patients showed reduced RSFC between Cere6.L and left cerebellar region IX and the left superior frontal gyrus (SFGdor.L). Both svMCI+D and svMCI-D groups showed increased RSFC between Cere6.L and the right caudate nucleus. RSFC between Cere6.L and SFGdor.L correlated negatively with HAMD scores in svMCI+D and positively with MoCA scores in svMCI-D. RSFC between Cere6.L and the right caudate nucleus also correlated positively with MoCA in the svMCI-D. Cerebellar abnormalities, including the gray matter atrophy and RSFC changes, are associated with svMCI, particularly when depression symptoms are present. These results suggest potential diagnostic and therapeutic implications for svMCI and emphasize the need for further research on the cerebellum's role in cognitive and emotional disorders.

CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation

Microglia are heterogeneous macrophage cells that serve as the central nervous system’s resident immune cells. During neuro-related diseases, CNS resident macrophages change their molecular, cellular, and functional properties—that collectively define “states”—in response to specific neural perturbations. Neurovascular diseases elicit state changes, by promoting increased vascular permeability among microvessels and thus altering blood–brain barrier integrity. Here, we used a mouse model of brain arteriovenous malformation (bAVM)—mediated by endothelial loss of Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)—to investigate changes to brain resident macrophage states during neurovascular disease pathogenesis. We found increased area of Ionized calcium-binding adapter molecule 1 (Iba1) expression in Rbpj-deficient bAVM tissue, as well as Iba1 + cell hypertrophy, increased cell number, and hyperproliferation within areas of increased Iba1 + density. Hypertrophic cells had increased cell body areas and decreased process length, suggesting a transition in surveillance state. Gene expression data revealed region-specific molecular changes to Iba + cells, suggestive of altered metabolic activity. CNS resident macrophages isolated from cortical and cerebellar regions showed profiles consistent with cytokine-associated immunogenic responses and an immunovigilant pathogen-recognition response, respectively. Thus, our findings demonstrate region-specific changes to CNS resident macrophages during Rbpj-deficient bAVM.

Imaging characteristics of brain microstructure and cerebral perfusion in Crohn's disease patients with anxiety: A prospective comparative study.

Anxiety is a common comorbidity in patients with Crohn's disease (CD). Data on the imaging characteristics of brain microstructure and cerebral perfusion in CD with anxiety are limited. To compare the imaging characteristics of brain microstructure and cerebral perfusion among CD patients with or without anxiety and healthy individuals. This prospective comparative study enrolled consecutive patients with active CD and healthy individuals who visited the study hospital between January 2022 and January 2023. Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety. The imaging characteristics of brain microstructure and cerebral perfusion were measured by diffusion kurtosis imaging and intravoxel incoherent motion. A total of 57 participants were enrolled. Among the patients with active CD, 16 had anxiety. Compared with healthy individuals, patients with active CD demonstrated significantly lower radial kurtosis values in the right cerebellar region 6, lower axial kurtosis (AK) values in the right insula, left superior temporal gyrus, and right thalamus, and higher slow and fast apparent diffusion coefficients (ADCslow and ADCfast) in the bilateral frontal lobe, bilateral temporal lobe, and bilateral insular lobe (all P < 0.05). Compared with patients with CD without anxiety, patients with CD and anxiety exhibited significantly higher ADCslow values in the left insular lobe and lower AK values in the right insula and right anterior cuneus (all P < 0.05). There are variations in brain microstructure and perfusion among CD patients with/without anxiety and healthy individuals, suggesting potential use in assessing anxiety-related changes in active CD.

Association between resting-state synaptic activity and overall performance in a cognitive visuoconstructive task as revealed by magnetoencephalography (MEG).

Performance of a task involves the engagement of various brain areas, as evidenced by the effects of lesions of particular brain areas and the results of functional neuroimaging and neurophysiological studies. Here we tested the hypothesis that overall task performance would depend on the level of ongoing, resting-state change in synaptic activity of participating areas, such that the degree of success of the outcome would be higher, the higher the resting-state activation. For that purpose, we used 248-sensor magnetoencephalography (MEG) in healthy people to obtain estimates of resting-state synaptic activity in various areas and then correlated those estimates to the average performance score in three visuospatial tasks assessed outside the MEG session using the Montreal Cognitive Assessment (MoCA), namely the Trails, Cube, and Clock Drawing (TCCD) tasks. We found that the average success score in these tasks covaried positively with the level of resting-state neural activity of 3 broad area clusters, namely (a) right cerebellum, occipital, and parietal cortical regions (strongest association), (b) right inferior frontal, middle and posterior temporal regions, and (c) left middle frontal region. The dependence of the outcome of task performance on the activation state of areas in the absence of action, i.e. in resting-state, points to a priming role in facilitating task performance.

Cerebellar Volume Measures Differentiate Multiple Sclerosis Fallers from Non-Fallers.

The cerebellum is a common lesion site in persons with multiple sclerosis (PwMS). Physiologic and anatomic studies have identified a topographic organization of the cerebellum including functionally distinct motor and cognitive areas. In this study, a recent parcellation algorithm was applied to a sample of PwMS and healthy controls to examine the relationships among specific cerebellar regions, fall status, and common clinical measures of motor and cognitive functions. Thirty-one PwMS and twenty-nine age- and sex-matched controls underwent an MRI scan and motor and cognitive testing. The parcellation algorithm was applied to all images and divided the cerebellum into 28 regions. Mann-Whitney U tests were used to compare cerebellar volumes among PwMS and controls, and MS fallers and MS non-fallers. Relationships between cerebellar volumes and motor and cognitive function were evaluated using Spearman correlations. PwMS performed significantly worse on functional measures compared to controls. We found significant differences in volumetric measures between PwMS and controls in the corpus medullare, lobules I-III, and lobule V. Volumetric differences seen between the PwMS and controls were primarily driven by the MS fallers. Finally, functional performance on motor and cognitive tasks was associated with cerebellar volumes. Using the parcellation tool, our results showed that the volumes of motor and cognitive lobules impact both motor and cognitive performance, and that functional performance and cerebellar volumes distinguishes the MS fallers from non-fallers. Future studies should explore the potential of cerebellar imaging to predict falls in PwMS.

Altered Intracerebellar Functional Connectivity in Friedreich’s Ataxia: A Graph-Theory Functional MRI Study

Historically, Friedreich’s Ataxia (FRDA) has been linked to a relatively preserved cerebellar cortex. Recent advances in neuroimaging have revealed altered cerebello-cerebral functional connectivity (FC), but the extent of intra-cerebellar FC changes and their impact on cognition remains unclear. This study investigates intra-cerebellar FC alterations and their cognitive implications in FRDA. In this cross-sectional, single-center study, resting-state functional MRI data from 17 patients with FRDA (average age 27.7 ± 13.6 years; F/M = 6/11) and 20 healthy controls (HC) (average age 29.4 ± 9.7 years; F/M = 9/11), all of whom underwent neuropsychological testing, were analyzed. From functional connectivity matrices, graph measures were computed at both the network and node levels using two complementary parcellations. FRDA patients exhibited decreased global efficiency (p = 0.04), nodal degree (p = 0.001) and betweenness centrality (p = 0.04) in the vermal portion of lobule VIII, along with reduced global efficiency in cerebellar regions belonging to the Control-A network (p = 0.02), one of the three subdivisions of the Frontoparietal network. Verbal memory deficits correlated with global efficiency in both the vermal portion of lobule VIII (r = 0.53, p = 0.02) and the cerebellar regions of the Control-A network (r = 0.49, p = 0.05). Graph analysis revealed regional intra-cerebellar FC changes in FRDA, marked by reduced functional centrality in cerebellar regions of the vermis and responsible for executive functions. These changes correlated with cognitive alterations, highlighting the role of the cerebellar cortex in the cognitive impairment observed in FRDA.

Whole-brain functional connectivity and structural network properties in stroke patients with hemiplegia.

This study explored structural and functional alterations in the whole brain of stroke patients with hemiplegia. We collected multimodal magnetic resonance images of 24 patients with ischaemic stroke and 16 age-matched controls. Resting-state functional connectivity (FC) for all brain regions was evaluated. Diffusion tensor imaging was used to construct white matter structural networks, and the graph properties of the structural network were analysed using graph theory to determine group differences. The ipsilesional posterior parietal cortex (PPC) in the frontoparietal network accounts for more than half of the 25 brain regions with altered FC in stroke patients. The nodal efficiency of multiple ipsilesional frontal lobes and cerebellar regions, such as the ipsilateral cerebellum 8, was reduced. The contralesional cerebellum 8 showed elevated FC with the lingual gyrus and the visual network. Our results suggest that the PPC and cerebellum 8 are regions worthy of in-depth study. The cerebellum 8 may supplement deficits in motor balance function by enhancing functional congruence with the visual area. This study identified key brain regions and characteristics that exhibit structural and functional changes following stroke injury.

Poststroke Translocator Protein Expression Dynamics and Correlations to Chronic Infarction: A [123I]-CLINDE-SPECT Study.

This study aims to investigate the longitudinal changes in translocator protein (TSPO) following stroke in different brain regions and potential associations with chronic brain infarction. Twelve patients underwent SPECT using the TSPO tracer 6-Chloro-2-(4'-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide, as well as structural MRI, at 10, 41, and 128days (median) after ischemic infarction in the middle cerebral artery. TSPO expression was measured in lesional (MRI lesion and SPECT lesion), connected (pons and ipsilesional thalamus), and nonconnected (ipsilesional cerebellum and contralesional occipital cortex) regions. Correlations were explored between the volume of chronic infarction and TSPO expression in nonconnected regions of interest (ROIs) at 128days RESULTS: Throughout the study period, TSPO levels decreased by 24%-33% in lesional ROIs, while levels increased in connected ROIs by 35%-69% and in nonconnected ROIs by 53%-77%. At 128days poststroke, TSPO expression in ipsilesional cerebellum positively correlated with chronic infarction volume (p=0.002, r2=0.72). This study expands the current knowledge of spatial and temporal TSPO expression in humans by quantifying TSPO changes in lesional, connected, and nonconnected brain regions at three time points after cerebral infarction as well as correlating late-stage TSPO upregulation and chronic infarction volume.

Posterior Reversible Encephalopathy Syndrome:&amp;nbsp; Two Cases of a Rare Complication of Hypertensive Disorders in Pregnancy

Hypertensive disorders in pregnancy are one of the leading causes of maternal and foetal morbidity and mortality. One of the rarest complications of preeclampsia and eclampsia is Posterior Reversible Encephalopathy Syndrome (PRES) also known as reversible posterior leukoencephalopathy syndrome. We report two cases of PRES occurring during pregnancy, characterised by headache and visual symptoms in the setting of preeclampsia. MRI brain scans showed involvement of the occipital, parietal, and cerebellar regions in both cases. One patient also had hypertensive retinopathy and optic disc haemorrhages. Multidisciplinary management included controlling high blood pressure, delivery, and follow-up care. Both patients recovered over weeks without permanent residual effects.

Metabolic connectivity of freezing in Parkinson's disease

Background Freezing of gait (FoG) is among the most disabling gait disorders of Parkinson's disease. The full understanding of its mechanisms requires a network study approach. So far, FoG was mainly studied using magnetic resonance imaging, and especially using the resting state functional sequence, which does not completely reflect the brain actual modifications. Objective This study aims to investigate metabolic networks using position emission tomography (PET) imaging. Exploration after a rest or gait session combined with a delayed tracer's uptake are assumed to reflect the actual metabolism modifications. Methods Twenty-six patients in the off-drug state underwent two PET imaging sessions using [18F]- fluorodeoxyglucose, the first after 30 min of rest (rest condition) and the second after 30 min of real gait (gait condition). Twelve patients presented real FoG during cerebral glucose uptake. Brain connectivity matrices were measured for each group and condition, and then compared. Results In the rest condition, the freezing group showed globally reduced metabolic connectivity between brain regions compared to the non-freezing group. During gait, enhanced connectivity was observed in the cerebellum, cerebello-cortical loops and parieto-frontal regions, with high recruitment of the visual cortex in the freezing group. However, connectivity inside cerebellar networks remained lower in the freezing group than in the non-freezing group, while occipito-frontal connectivity was higher in the freezing group. Conclusions Studying real freezing of gait in a vertical position emphasized the role of the visual cortex and cerebellum in gait problems.

Neuropathological correlates of vulnerability and resilience in the cerebellum in Alzheimer's disease.

We investigated whether the cerebellum develops neuropathology that correlates with well-accepted Alzheimer's disease (AD) neuropathological markers and cognitive status. We studied cerebellar cytoarchitecture in a cohort (N=30) of brain donors. In a larger cohort (N=605), we queried whether the weight of the contents of the posterior fossa (PF), which contains primarily cerebellum, correlated with dementia status. Although there was no granular layer (GL) cell loss, GL area was lower in AD cases, particularly in the lateral cerebellum. Lower numbers of mossy fiber synaptic terminals in the cerebellar GL of AD cases correlated with Braak stages IV-VI. PF content weight correlated with dementia independently of age, neuropathology, and education. In addition, we found that a measure of the relative size of the PF content weight to total brain weight correlated with less dementia. These results confirm that the cerebellum is not spared neuropathological damage in AD. Novel evidence of cerebellar atrophy in the granule cell layer of the lateral cerebellar cortex (or 'cognitive cerebellum'), and loss of a specific cerebellar synapse type in this region, the cerebellar glomerulus. Both correlated with dementia status and Braak stages IV through VI, in a cohort with complete neuropathological characterization. Although there have been recent brain imaging studies suggesting a role for cerebellum in Alzheimer's disease, we believe our study constitutes some of the most concrete neuropathological evidence to date of anatomic and synaptic substrates that are disrupted in AD. These changes in this cerebellar region may even play a role in the etiology of cognitive symptoms. Novel evidence that individuals with lower postmortem cerebellar weights showed more cognitive decline, independent of classical neuropathology markers such as Braak stage, Thal phase, or Corsortium to Establish a Registry for Alzheimer's Disease (CERAD) score, suggesting a role for this brain region in dementia, using advanced statistical analysis of a large unbiased population cohort (n=605), the Adult Changes in Thought (ACT) study. Conversely, a measure of how intact the cerebellum was correlated with less dementia, independent of classical neuropathology markers and cerebral cortical weight, again, in the ACT cohort of 605 brain donors. We believe that this novel finding has relevance and implications for the identification of resilience factors, which may protect against the development of dementia.

Metabolomic Profile Modification in the Cerebellum of Mice Repeatedly Exposed to Khat and Treated with β-Lactamase Inhibitor, Clavulanic Acid.

Catha edulis, commonly known as khat, is used for its psychoactive effects and is considered a natural amphetamine. The current study investigated the metabolomic profile in the cerebellum of mice after repeated exposure to khat and evaluated the effects of clavulanic acid on the metabolomic profile in the cerebellum in khat-treated mice. Male C67BL/6 mice that were 6-9 weeks old were recruited and divided into three groups: the control group was treated with 0.9% normal saline for 17 days; the khat group was given khat extract at a dose of 360 mg/kg via the intraperitoneal (i.p) route for 17 days; and another khat group was treated with khat for 17 days and clavulanic acid at a dose of 5 mg/kg for the last 7 days (days 11-17). At the end of the 17th day, the animals were sacrificed, and their brains were immediately collected and stored at -80 °C. The cerebellum region of the brain was isolated in each group by micropuncture using cryostat and underwent a metabolomics study via Gas Chromatography/Mass Spectroscopy (GC/MS). The total peak area ratios of the selected metabolites in the cerebellum after repeated exposure to the khat extract were significantly reduced (p < 0.05) and treatment of the khat group with clavulanic acid significantly increased (all p < 0.05) the total peak areas ratios of the selected metabolites when compared to their corresponding areas in the alternative khat group. These levels of selected metabolites were further confirmed by observing the metabolite peak area ratios and performing a heat map analysis and a principal compartment analysis of the samples in the cerebellum. A network analysis of altered metabolites in the cerebellum showed a strong correlation between the different metabolites, which showed that an increase in one metabolite can modulate the levels of others. An analysis using the MetaboAnalyst software revealed the involvement of selected altered metabolites like lactic acid in many signaling pathways, like gluconeogenesis, while enrichment analysis data showed altered pathways for pyruvate metabolism and disease pathogenesis. Finally, a network analysis showed that selected metabolites were linked with other metabolites, indicating drug-drug interactions. The present study showed that repeated exposure of mice to khat altered the levels of various metabolites in the cerebellum which are involved in the pathogenesis of different diseases, signaling pathways, and interactions with the pharmacokinetic profile of other therapeutic drugs. The treatment of khat-treated mice with clavulanic acid positively modified the metabolomics profile in the cerebellum and increased the levels of the altered metabolites.

Interpolation of Imaging Mass Spectrometry Data by a Window-Based Adversarial Autoencoder Method.

Imaging mass spectrometry (IMS) is a technique for simultaneously acquiring the expression and distribution of molecules on the surface of a sample, and it plays a crucial role in spatial omics research. In IMS, the time cost and instrument load required for large data sets must be considered, as IMS typically involves tens of thousands of pixels or more. In this study, we developed a high-resolution method for IMS data reconstruction using a window-based Adversarial Autoencoder (AAE) method. We acquired IMS data from partial cerebellum regions of mice with a pitch size of 75 μm and then down-sampled the data to a pitch size of 150 μm, selecting 22 m/z peak intensity values per pixel. We established an AAE model to generate three pixels from the surrounding nine pixels within a window to reconstruct the image data at a pitch size of 75 μm. Compared with two alternative interpolation methods, Bilinear and Bicubic interpolation, our window-based AAE model demonstrated superior performance on image evaluation metrics for the validation data sets. A similar model was constructed for larger mouse kidney tissues, where the AAE model achieved high image evaluation metrics. Our method is expected to be valuable for IMS measurements of large animal organs across extensive areas.

Microstructural Alterations of Cerebellar Peduncles in Relapsing Remitting Multiple Sclerosis: a Systematic Review and Meta-Analysis of Diffusion Tensor Imaging Studies.

Damage to cerebellar peduncles is common in patients with relapsing-remitting multiple sclerosis (RRMS). This can lead to a diverse range of motor and cognitive disabilities. Here, we aimed to evaluate the quantitative alterations of cerebellar peduncles using diffusion tensor imaging (DTI).After a comprehensive search in Web of Science, PubMed, Embase, and Scopus and a rigorous screening, eligible studies underwent data extraction and risk of bias assessment. Standardized Mean Difference (SMD) with a 95% CI was used as effect size. We compared DTI metrics in the cerebellar peduncle regions (SCP, MCP, ICP) between RRMS patients and healthy controls (HC). Sensitivity analysis employed the leave-one-out method. Contour-enhanced funnel plots and Pustejovsky test were used to evaluate the publication bias. Additionally, subgroup analysis was performed using available variables.In eleven included studies encompassing 623 RRMS patients and 416 HC, RRMS patients exhibited significantly decreased fractional anisotropy (FA) values in the SCP (SMD - 0.26) and MCP (SMD - 1.03), increased mean diffusivity (MD) values in the SCP (SMD 1.46), MCP (SMD 0.48) and ICP (SMD 0.70), elevated radial diffusivity (RD) values in the MCP (SMD 0.85) and ICP (SMD 1.20) compared to HC. The subgroup analysis revealed that individuals with elevated EDSS scores exhibited reduced FA and increased MD in the SCP region. No considerable publication bias was detected. No outliers were detected in the sensitivity analysis.DTI proves promising for identifying microstructural abnormalities in cerebellar peduncles of RRMS patients, with decreased FA and increased RD, and MD values observed.

Electroacupuncture Mitigates TRPV1 Overexpression in the Central Nervous System Associated with Fibromyalgia in Mice.

Fibromyalgia (FM) is characterized by chronic pain, significantly affecting the quality of life and functional capabilities of patients. In addition to pain, patients may experience insomnia, chronic fatigue, depression, anxiety, and headaches, further complicating their overall well-being. The Transient Receptor Potential Vanilloid 1 (TRPV1) receptor responds to various noxious stimuli and plays a key role in regulating pain sensitivity and inflammation. Thus, targeting TRPV1 may provide analgesic and anti-inflammatory benefits. This study investigates the efficacy of electroacupuncture (EA) in alleviating chronic pain in FM through TRPV1 and its downstream molecules in the central nervous system (CNS). To model FM, we subjected mice to intermittent cold stress (ICS) for three days. The study comprised five rodent groups: Control (CON), ICS, ICS + EA, ICS + Sham EA, and ICS + KO (TRPV1 knockout mice). Our findings revealed that ICS induced allodynia and hyperalgesia in mice by day four, persisting until day 21. EA at 2 Hz and TRPV1 KO significantly decreased both mechanical and thermal hypersensitivity (Withdrawal-Day 14: 2.43 ± 0.19 g; Day 21: 5.88 ± 0.47 g, n = 6, p < 0.05; Latency-Day 14: 2.77 ± 0.22 s; Day 21: 5.85 ± 0.41 s, n = 6, p < 0.05). In contrast, sham EA did not produce significant effects. Additionally, TRPV1 and several pain-related proteins were significantly elevated in the thalamus, somatosensory cortex (SSC), medial prefrontal cortex (mPFC), hippocampus, hypothalamus, cerebellum regions V (CB V), VI (CB VI) and VII (CB VII) after the ICS model. Both EA at the ST36 acupoint and TRPV1 KO mice showed diminished overexpression of pain-related proteins, with the sham EA group showing no significant changes compared to the ICS group. Chronic widespread pain was reduced by EA and TRPV1 KO, with the effects of EA on the TRPV1 pain pathway clearly evident in the CNS after 21 days.