Brain Cortex Research Articles

Association of Unc-51-like Kinase 4 (ULK4) with the reactivity of the extended reward system in response to conditioned stimuli

Objectives ULK4 is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the ULK4 locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm. Methods Two hundred and thirty-four patients were included in this study. Association of genetic variation in the ULK4 gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli. Results Variant prioritisation revealed the strongest functional signatures for the ULK4 variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system. Conclusions Our findings provide further evidence in humans that genetic variation in ULK4 may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.

Current progress on characteristics of intracranial electrophysiology related to prolonged disorders of consciousness

Prolonged disorders of consciousness (pDOC) are pathological conditions of alterations in consciousness caused by various severe brain injuries, profoundly affecting patients' life ability and leading to a huge burden for both the family and society. Exploring the mechanisms underlying pDOC and accurately assessing the level of consciousness in the patients with pDOC provide the basis of developing therapeutic strategies. Research of non-invasive functional neuroimaging technologies, such as functional magnetic resonance (fMRI) and scalp electroencephalography (EEG), have demonstrated that the generation, maintenance and disorders of consciousness involve functions of multiple cortical and subcortical brain regions, and their networks. Invasive intracranial neuroelectrophysiological technique can directly record the electrical activity of subcortical or cortical neurons with high signal-to-noise ratio and spatial resolution, which has unique advantages and important significance for further revealing the brain function and disease mechanism of pDOC. Here we reviewed the current progress of pDOC research based on two intracranial electrophysiological signals, spikes reflecting single-unit activity and field potential reflecting multi-unit activities, and then discussed the current challenges and gave an outlook on future development, hoping to promote the study of pathophysiological mechanisms related to pDOC and provide guides for the future clinical diagnosis and therapy of pDOC.

Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography

BackgroundAutism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits.MethodsWe used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models.ResultsWe found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits.LimitationsOptical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism.ConclusionsThis study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits.

Quantitative and Radiological Assessment of Post-cardiac-Arrest Comatose Patients with Diffusion-Weighted Magnetic Resonance Imaging.

Although magnetic resonance imaging, particularly diffusion-weighted imaging, has increasingly been used as part of a multimodal approach to prognostication in patients who are comatose after cardiac arrest, the performance of quantitative analysis of apparent diffusion coefficient (ADC) maps, as compared to standard radiologist impression, has not been well characterized. This retrospective study evaluated quantitative ADC analysis to the identification of anoxic brain injury by diffusion abnormalities on standard clinical magnetic resonance imaging reports. The cohort included 204 previously described comatose patients after cardiac arrest. Clinical outcome was assessed by (1) 3-6 month post-cardiac-arrest cerebral performance category and (2) coma recovery to following commands. Radiological evaluation was obtained from clinical reports and characterized as diffuse, cortex only, deep gray matter structures only, or no anoxic injury. Quantitative analyses of ADC maps were obtained in specific regions of interest (ROIs), whole cortex, and whole brain. A subgroup analysis of 172 was performed after eliminating images with artifacts and preexisting lesions. Radiological assessment outperformed quantitative assessment over all evaluated regions (area under the curve [AUC] 0.80 for radiological interpretation and 0.70 for the occipital region, the best performing ROI, p = 0.011); agreement was substantial for all regions. Radiological assessment still outperformed quantitative analysis in the subgroup analysis, though by smaller margins and with substantial to near-perfect agreement. When assessing for coma recovery only, the difference was no longer significant (AUC 0.83 vs. 0.81 for the occipital region, p = 0.70). Although quantitative analysis eliminates interrater differences in the interpretation of abnormal diffusion imaging and avoids bias from other prediction modalities, clinical radiologist interpretation has a higher predictive value for outcome. Agreement between radiological and quantitative analysis improved when using high-quality scans and when assessing for coma recovery using following commands. Quantitative assessment may thus be more subject to variability in both clinical management and scan quality than radiological assessment.

Altered local intrinsic neural activity and molecular architecture in internet use disorders

BackgroundInternet gaming disorder (IGD) is mainly characterized by its core dysfunction in higher-order brain cortices involved in inhibitory control, whose neurobiological basis remains unclear. Then, we will investigate local intrinsic neural activity (INA) alterations in IGD, ascertain whether these potential alterations are related to clinical characteristics, and further explore the underlying molecular architecture. MethodIn this study, we performed the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) derived from resting-state functional magnetic resonance imaging (rs-fMRI) to explore the impact of IGD on local INA. Correlation analysis revealed the relationship between ReHo and fALFF in terms of group differences and clinical characteristics. Moreover, correlations between fALFF, ReHo, and PET- and SPECT-driven maps were investigated to elucidate the specific molecular architecture alternations in IGD. Finally, receiver operating characteristic curve (ROC) analysis was used to show the potential abilities of fALFF and ReHo in distinguishing individuals with IGD (IGDs) from healthy controls (HCs). ResultCompared with HCs, IGDs revealed increased ReHo and fALFF in the prefrontal cortex. Significantly decreased ReHo was observed in the temporal lobe, occipital lobe, and cerebellum. In addition, the ReHo values in the cerebellum_7b_R were positively correlated with internet addiction severity. ROC curve analysis showed that ReHo and fALFF-altered brain regions could effectively distinguish IGDs from HCs. More importantly, cross-modal correlations revealed local INA changes in brain regions associated with the monoamine neurotransmitter system and the less studied cholinergic/GABAergic system. ConclusionThese results suggest that local functional impairments are shown in the audiovisual and inhibitory control circuits in IGDs. This may be associated with underlying neurotransmitter system alterations. Therefore, this study provides the possibility of GABAergic receptor agonists and cholinergic receptor inhibitors for the treatment of IGD.

Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington disease models.

Huntington disease (HD) is a fatal neurodegenerative disease caused by a trinucleotide repeat expansion in exon 1 of the huntingtin gene (HTT) resulting in toxic gain-of-function and cell death. Despite its monogenic cause, the pathogenesis of HD is highly complex and increasing evidence indicates that, in addition to the full-length (FL) mutant HTT protein, the expanded exon 1 HTT (HTTexon1) protein that is translated from the HTT1a transcript generated by aberrant splicing is prone to aggregate and may contribute to HD pathology. This finding suggests that reducing the expression of HTT1a may achieve a greater therapeutic benefit than targeting only FL mutant HTT. Conversely, strategies that exclusively target FL HTT may not fully prevent the pathogenesis of HD. We have developed an engineered microRNA targeting the HTT exon 1 sequence (miHTT), delivered via adeno-associated virus serotype 5 (AAV5). The target sequence of miHTT is present in both FL HTT and HTT1a transcripts. Preclinical studies with AAV5-miHTT have demonstrated efficacy in several rodent and large animal models by reducing FL HTT mRNA and protein and rescuing HD-like phenotypes, and have been the rationale for phase I/II clinical studies now ongoing in the US and Europe. In the present study, we evaluated the ability of AAV5-miHTT to reduce the levels of aberrantly spliced HTT1a mRNA and the HTTexon1 protein in the brain of two mouse models of HD (heterozygous zQ175 knock-in mice and humanized Hu128/21 mice). Polyadenylated HTT1a mRNA and HTTexon1 protein were detected in the striatum and cortex of heterozygous zQ175 knock-in mice, but not in wild-type, littermate control mice. Intrastriatal administration of AAV5-miHTT resulted in dose-dependent expression of mature miHTT microRNA in cortical brain regions, accompanied by significant lowering of both FL HTT and HTT1a mRNA expression at two months post-injection. Mutant HTT and HTTexon1 protein levels were also significantly reduced in the striatum and cortex of heterozygous zQ175 knock-in at 2 months after AAV5-miHTT treatment and in humanized Hu128/21 mice 7 months post-treatment. The effects were confirmed in primary Hu128/21 neuronal cultures. These results demonstrate that AAV5-miHTT gene therapy is an effective approach to lower both FL HTT and the pathogenic HTTexon1 levels, which could potentially have an additive therapeutic benefit compared to other HTT-targeting modalities.

Prenatal chlorpyrifos and pyrethroid exposure and children’s cortical brain activation in the ISA birth cohort, Costa Rica: an exploratory study

Prenatal chlorpyrifos and pyrethroid exposure and children’s cortical brain activation in the ISA birth cohort, Costa Rica: an exploratory study

Cortical response characteristics of passive, active, and resistance movements: a multi-channel fNRIS study.

This study aimed to explore the impact of exercise training modes on sensory and motor-related cortex excitability using functional near-infrared spectroscopy technology (fNIRS) and reveal specific cortical effects. Twenty participants with no known health conditions took part in a study involving passive, active, and resistance tasks facilitated by an upper-limb robot, using a block design. The participants wore functional near-infrared spectroscopy (fNIRS) devices throughout the experiment to monitor changes in cortical blood oxygen levels during the tasks. The fNIRS optode coverage primarily targeted key areas of the brain cortex, including the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and premotor cortex (PMC) on both hemispheres. The study evaluated cortical activation areas, intensity, and lateralization values. Passive movement primarily activates M1 and part of S1, while active movement mainly activates contralateral M1 and S1. Resistance training activates brain regions in both hemispheres, including contralateral M1, S1, SMA, and PMC, as well as ipsilateral M1, S1, SMA, and PMC. Resistance movement also activates the ipsilateral sensorimotor cortex (S1, SMA, PMC) more than active or passive movement. Active movement has higher contralateral activation in M1 compared to passive movement. Resistance and active movements increase brain activity more than passive movement. Different movements activate various cortical areas equally on both sides, but lateralization differs. The correlation between lateralization of brain regions is significant in the right cortex but not in the left cortex during three movement patterns. All types of exercise boost motor cortex excitability, but resistance exercise activates both sides of the motor cortex more extensively. The PMC is crucial for intense workouts. The right cortex shows better coordination during motor tasks than the left. fNIRS findings can help determine the length of treatment sessions.

Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease

IntroductionThe bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. MethodsThis study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. ResultsA total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. ConclusionThe detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging.

Synapses are implicated in many neuropsychiatric illnesses. Here, we provide an overview of in vivo techniques to index synaptic markers in patients. Several positron emission tomography (PET) tracers for synaptic vesicle glycoprotein 2 A (SV2A) show good reliability and selectivity. We review over 50 clinical studies including over 1700 participants, and compare findings in healthy ageing and across disorders, including addiction, schizophrenia, depression, posttraumatic stress disorder, and neurodegenerative disorders, including tauopathies, Huntington's disease and α-synucleinopathies. These show lower SV2A measures in cortical brain regions across most of these disorders relative to healthy volunteers, with the most well-replicated findings in tauopathies, whilst changes in Huntington's chorea, Parkinson's disease, corticobasal degeneration and progressive supranuclear palsy are predominantly subcortical. SV2A PET measures are correlated with functional connectivity across brain networks, and a number of other measures of brain function, including glucose metabolism. However, the majority of studies found no relationship between grey matter volume measured with magnetic resonance imaging and SV2A PET measures. Cognitive dysfunction, in domains including working memory and executive function, show replicated inverse relationships with SV2A measures across diagnoses, and initial findings also suggest transdiagnostic relationships with mood and anxiety symptoms. This suggests that synaptic abnormalities could be a common pathophysiological substrate underlying cognitive and, potentially, affective symptoms. We consider limitations of evidence and future directions; highlighting the need to develop postsynaptic imaging markers and for longitudinal studies to test causal mechanisms.

Proteomic Characterization of Changes in Mouse Brain Cortex Protein Expression at Different Post-Mortem Intervals: A Preliminary Study for Forensic Biomarker Identification.

Accuracy in the evaluation of death-induced tissue degradation for thanato-chronological purposes is strictly dependent on the condition of the biological source as well as on the precision of post-mortem interval (PMI) estimation. Thus, the optimization of tissue handling and identification of sensitive post-mortem biomarkers could help establish a timeline for post-mortem events. To this aim, we investigated the proteome changes in cortex samples of 6-week-old female SAMR1 mice over a post-mortem time course. After death, brain tissue was removed immediately (T0), and after 4, 8, 12, 24, and 32 h, four mice were used for each time period, and animals were maintained at 4 °C until brain removal. Dissected tissues were frozen at -80 °C until processed. Proteomic analysis, performed on samples related to early and late PMIs (<24 h and >24 h post-mortem, respectively) showed protein level changes as compared to T0 samples, with a remarkable increase in Calpain11 in the early PMI, as well as in Caspases 7 and 8 together with Gasdermin 3 in late PMI. These findings were confirmed by LIFT mass spectrometry technology and western blot analysis and, although requiring further investigation in other biological samples, suggest that these proteins could be considered as putative biomarkers of different PMIs.

Scalp Acupuncture Synchronizing Dual Task Gait for Enhancing Prefrontal Cortex Response.

Studies have shown that motor-cognitive dual task can greatly improve motor/cognitive function. However, the therapeutic effect of motor-cognitive dual task is still limited. How to improve dual-task performance is the key to solving this problem. Scalp acupuncture is a non-drug intervention method of traditional Chinese medicine to treat brain-derived diseases by acupuncturing the corresponding projection area of cerebral cortex function on the scalp. Studies have shown that scalp acupuncture helps improve neuronal damage and cognitive dysfunction and plays a neuroprotective function in central nervous system diseases. However, no relevant studies have discussed the synergistic gain effect of motor-cognitive dual task and scalp acupuncture. Therefore, this protocol aims to demonstrate the standardized operation of scalp acupuncture synchronizing motor-cognitive dual task and motor-cognitive dual task and compares the differences between these two tasks in healthy subjects through a randomized cross-over trial. This protocol initially revealed the possible influence mechanism of scalp acupuncture synchronizing motor-cognitive dual task on cognitive performance, gait control, and cortical brain function, which can provide new ideas and a theoretical basis for clinical exploration of new and effective non-drug treatment of integrated Chinese and Western medicine.

Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

HIV transcription persists in the brain of virally suppressed people with HIV.

HIV persistence in the brain is a barrier to cure, and potentially contributes to HIV-associated neurocognitive disorders. Whether HIV transcription persists in the brain despite viral suppression with antiretroviral therapy (ART) and is subject to the same blocks to transcription seen in other tissues and blood, is unclear. Here, we quantified the level of HIV transcripts in frontal cortex tissue from virally suppressed or non-virally suppressed people with HIV (PWH). HIV transcriptional profiling of frontal cortex brain tissue (and PBMCs where available) from virally suppressed (n = 11) and non-virally suppressed PWH (n = 13) was performed using digital polymerase chain reaction assays (dPCR). CD68+ myeloid cells or CD3+ T cells expressing HIV p24 protein present in frontal cortex tissue was detected using multiplex immunofluorescence imaging. Frontal cortex brain tissue from PWH had HIV TAR (n = 23/24) and Long-LTR (n = 20/24) transcripts. Completion of HIV transcription was evident in brain tissue from 12/13 non-virally suppressed PWH and from 5/11 virally suppressed PWH, with HIV p24+CD68+ cells detected in these individuals. While a block to proximal elongation was present in frontal cortex tissue from both PWH groups, this block was more extensive in virally suppressed PWH. These findings suggest that the brain is a transcriptionally active HIV reservoir in a subset of virally suppressed PWH.

Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging.

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.

AnNoBrainer, An Automated Annotation of Mouse Brain Images using Deep Learning.

Annotation of multiple regions of interest across the whole mouse brain is an indispensable process for quantitative evaluation of a multitude of study endpointsin neuroscience digital pathology. Prior experience and domain expert knowledge are the key aspects for image annotation quality and consistency. At present, image annotation is often achieved manually by certified pathologists or trained technicians, limiting the total throughput of studies performed at neuroscience digital pathology labs. It may also mean that simpler and quicker methods of examining tissue samples are used by non-pathologists, especially in the early stages of research and preclinical studies. To address these limitations and to meet the growing demand for image analysis in a pharmaceutical setting, we developed AnNoBrainer, an open-source software tool that leverages deep learning, image registration, and standard cortical brain templates to automatically annotate individual brain regions on 2D pathology slides. Application of AnNoBrainer to a published set of pathology slides from transgenic mice models of synucleinopathy revealed comparable accuracy, increased reproducibility, and a significant reduction (~ 50%) in time spent on brain annotation, quality control and labelling compared to trained scientists in pathology. Taken together, AnNoBrainer offers a rapid, accurate, and reproducible automated annotation of mouse brain images that largely meets the experts' histopathological assessment standards (> 85% of cases) and enables high-throughput image analysis workflows in digital pathology labs.

Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

Ecklonia cava Ameliorates Cognitive Impairment on Amyloid β-Induced Neurotoxicity by Modulating Oxidative Stress and Synaptic Function in Institute of Cancer Research (ICR) Mice.

This study investigated the neuroprotective effect of 70% ethanol extract of Ecklonia cava (EE) in amyloid beta (Aβ)-induced cognitive deficit mice. As a result of analyzing the bioactive compounds in EE, nine compounds were identified using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In particular, the diekcol content was quantified by high-performance liquid chromatography with diode-array detection (DAD-HPLC). Biochemical analysis was performed on brain tissue to determine the mechanism of the cognitive function improvement effect of EE. The result showed that EE ameliorated learning and memory decline in behavioral tests on Aβ-induced mice. EE also attenuated oxidative stress by regulating malondialdehyde (MDA) content, reduced glutathione (GSH), and superoxide dismutase (SOD) levels. Similarly, EE also improved mitochondrial dysfunction as mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels. In addition, EE enhanced synapse function by modulating acetylcholine-related enzymes and synaptic structural proteins in the whole brain, hippocampus, and cerebral cortex tissues. Also, EE regulated Aβ-induced apoptosis and inflammation through the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, EE protected neurotoxicity by increasing brain-derived neurotrophic factor (BDNF) production. These results suggest that EE may be used as a dietary supplement for the prevention and treatment of Alzheimer's disease (AD).

Single-cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Trem2R47H Alzheimer's risk gene mutation.

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer's Disease. In this study, we analyze the impact of the Trem2R47H mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2R47H, 5xFAD and Trem2R47H; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression. Spatial transcriptomics and neuropathology data are analyzed using our custom pipeline to identify plaque and Trem2R47H-induced transcriptomic dysregulation. We initially analyzecell type-specific transcriptomic alterations induced by plaque proximity. Next, we analyze spatial distributions of disease associated microglia and astrocytes, and how they vary between 5xFAD and Trem2R47H; 5xFAD mouse models. Finally, we analyze the impact of the Trem2R47H mutationon neuronal transcriptomes. The Trem2R47H mutation induces consistent upregulation of Bdnf and Ntrk2 across many cortical excitatory neuron types, independent of amyloid pathology. Spatial investigation of genotype enriched subclusters identified spatially localized neuronal subpopulations reduced in 5xFAD and Trem2R47H; 5xFAD mice. Overall, our MERFISH spatial transcriptomics analysis identifies glial and neuronal transcriptomic alterations induced independently by 5xFAD and Trem2R47H mutations, impacting inflammatory responses in microglia and astrocytes, and activity and BDNF signaling in neurons.

A biodegradable and self-deployable electronic tent electrode for brain cortex interfacing

A biodegradable and self-deployable electronic tent electrode for brain cortex interfacing