Cortical excitability and the aging brain: toward a biomarker of cognitive resilience

Frontiers in Psychology, Год журнала: 2025, Номер 16

Опубликована: Фев. 18, 2025

This perspective article addresses the potential use of cortical excitability (CE) as an indicator cognitive health in aging people. Changes CE may be considered a sign resilience to decline old age. The authors describe research on and its link function older adults emphasize that it is promising, non-invasive measure healthy aging. They also address current challenges implementation, need for standardized measurement protocols possible future avenues research. If properly considered, could pave way early detection facilitate targeted interventions promote resilience.

Язык: Английский

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Rod-shaped microglia interact with neuronal dendrites to regulate cortical excitability in TDP-43 related neurodegeneration

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Abstract Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, mechanisms underlying this early dysregulation are not fully understood. Microglia, as principal immune cells central nervous system, have emerged important players sensing and regulating neuronal activity. Here we investigated role microglia motor circuits a mouse model TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording longitudinal vivo calcium imaging awake mice, observed hyperactivity at initial disease progression. Spatial single-cell RNA sequencing revealed that primary responders to hyperactivity. We further identified unique subpopulation microglia, rod-shaped which characterized by distinct morphology transcriptional profile. Notably, predominantly interact with dendrites excitatory synaptic inputs attenuate The elimination through TREM2 deficiency increased hyperactivity, exacerbated deficits, decreased survival rates rNLS8 mice. Together, our results suggest play neuroprotective attenuating related neurodegeneration.

Язык: Английский

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Brain–body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis

Nature Reviews Neurology, Год журнала: 2024, Номер 20(8), С. 475 - 494

Опубликована: Июль 4, 2024

Язык: Английский

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Effects of dry needling on spasticity, cortical excitability, and range of motion in a patient with multiple sclerosis: a case report

Journal of Medical Case Reports, Год журнала: 2024, Номер 18(1)

Опубликована: Март 24, 2024

Abstract Background Dry needling is an intervention used by physiotherapists to manage muscle spasticity. We report the effects of three sessions dry on ankle plantar flexor spasticity and cortical excitability in a patient with multiple sclerosis. Case presentation The was 40-year-old Iranian woman 11-year history study outcomes were measured modified Ashworth scale, transcranial magnetic stimulation parameters, active passive range motion. They assessed before (T0), after (T1), at 2-week follow-up (T2). Our result showed: scale improved T2 from, 2 1. resting motor threshold decreased from 63 61 57 T1 T2, respectively. single test evokes potential increased 76.2 78.3. short intracortical inhibition 23.6 35.4 T2. facilitation 52 76 dorsiflexion ROM ~ 10° 6° Conclusion This case presented sclerosis who underwent flexors severe spasticity, highlighted successful use management dorsiflexion, excitability. Further rigorous investigations are warranted, employing randomized controlled trials sufficient sample patients Trial registration IRCT20230206057343N1, registered 9 February 2023, https://en.irct.ir/trial/68454

Язык: Английский

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Resting-State EEG Oscillations in Amyotrophic Lateral Sclerosis (ALS): Toward Mechanistic Insights and Clinical Markers

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 545 - 545

Опубликована: Янв. 16, 2025

Introduction: Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder characterized by the degeneration of motor neurons in brain, brainstem, and spinal cord. Several neuroimaging techniques can help reveal pathophysiology ALS. One these electroencephalogram (EEG), noninvasive relatively inexpensive tool for examining electrical activity brain with excellent temporal precision. Methods: This mechanistic review examines pattern resting-state EEG activity. With focus on publications published between January 1995 October 2024, we carried out comprehensive search 2024 across number databases, including PubMed/Medline, Research Gate, Google Scholar, Cochrane. Results: The literature yielded 17 studies included this review. varied significantly their methodology patient characteristics. Despite this, common biomarker typical ALS was found-reduced alpha power. Regarding other oscillations, findings are less consistent sometimes contradictory. As review, three possible explanations provided. main most important one increased cortical excitability. In addition, due to limitations studies, recommendations future research topic outlined enable further better understanding patterns Conclusions: Most showed power deficits patients, reflecting pathological hyperexcitability cerebral cortex. Future should address methodological identified small sample sizes, inconsistent frequency-band definitions, insufficient functional outcome measures, solidify extend current findings.

Язык: Английский

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The Effect of Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex on the Amyotrophic Lateral Sclerosis Patients With Cognitive Impairment: A Double‐Blinded, Randomized, and Sham Control Trial

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(3)

Опубликована: Март 1, 2025

ABSTRACT Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. A large number of ALS patients have cognitive impairment. In this double‐blinded, randomized, and sham‐controlled study, we aimed to investigate the effect repetitive transcranial magnetic stimulation (rTMS) on with Methods total 90 impairment were recruited from two cohorts; 80 participants randomly assigned in 1:1 ratio receive 10 Hz rTMS or sham treatment bilateral dorsolateral prefrontal cortices (DLPFC) for 4 consecutive weeks. The assessed by ECAS ALSFRS‐R scales. Zarit care burden scale was administered caregivers patients. primary outcome measured rate decline score between pretreatment, 6 months post‐treatment, 12 post‐treatment. Secondary outcomes included group difference slope score, neurofilament light chain plasma levels. Results intention‐to‐treat population significantly changed 79.74 ± 6.39 81.98 6.51 79.22 6.50 intervention at 6‐month 12‐month follow‐ups, respectively ( p = 0.031, 0.042). also decreased 57.65 3.42 52.24 3.34 56.42 3.41 3‐month post‐treatment time points, 0.003, 0.014). No significant differences observed groups other secondary endpoints. However, there trend decreasing NF‐L level rates over first months' follow‐up. Conclusions could yield short‐term positive effects subgroup alleviate caregivers' burden. improvement severity biomarkers.

Язык: Английский

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Targeting senescence in Amyotrophic Lateral Sclerosis: senolytic treatment improves neuromuscular function and preserves cortical excitability in a TDP-43Q331K mouse model.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary cortex (PMC) and spinal cord. Aging key factor ALS onset progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging ALS. This promotes senescent cell accumulation-marked irreversible cell-cycle arrest, impaired apoptosis, chronic inflammation-disrupting tissue homeostasis impairing neuronal support functions. Thus, targeting senescence presents novel therapeutic strategy for Here, we investigated senolytic combination Dasatinib Quercetin (D&Q) TDP-43 Q331K mice. D&Q improved neuromuscular function reduced plasma neurofilament light chain, biomarker of axonal damage. The most pronounced improvement was cortical excitability, accompanied reductions PMC. These findings highlight potential senolytics to mitigate ALS-related dysfunction, supporting their viability as strategy. *Jose A. Viteriab, Nathan R. Kerrab, Charles D. Brennana are co-first authors.

Язык: Английский

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The effect of toluene exposure on the fine structure of motor cortex pyramidal neurons in different aged rats: an electron microscopy study

Micron, Год журнала: 2025, Номер 195, С. 103833 - 103833

Опубликована: Апрель 15, 2025

Язык: Английский

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Safety and efficacy evaluation of intracerebroventricular human neural stem cell transplantation in SOD1 mice as a novel approach for ALS

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 9, 2025

Abstract Background Neural stem cell (NSC) transplantation holds promising therapeutic potential for neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). However, pre-clinical studies and early-phase clinical trials have faced challenges hindering the effective translation of this approach. Crucial hurdles include side-effects prolonged immunosuppression, concerns regarding origin dosage, identification most appropriate window, invasiveness surgical procedures. Here, we assessed safety efficacy intracerebroventricular (ICV) hNSC as a novel possibly more experimental approach ALS. Methods We evaluated administering up to 1 × 10 6 hNSCs in immunodeficient mice their reducing ALS hallmarks employing SOD1 G93A mouse model. Both transient (15 days) immunosuppression regimens, at low mg/kg) high (30 doses, were tested along with two different dosages (3 5 ). Results Our study suggests that: (i) bilateral ICV is safe non-tumorigenic hosts; (ii) sustained high-dose essential ensuring survival immunocompetent mice; (iii) may delay motor symptom progression reduce spinal cord microgliosis when administered ventricles under immunosuppression. Conclusions emerges strategy ALS, demonstrating decline microgliosis. crucial efficacy, emphasizing need further optimization overcome translational achieve durable benefits.

Язык: Английский

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Glutamatergic Regulation of miRNA‐Containing Intraluminal Vesicle Trafficking and Extracellular Vesicle Secretion From Cortical Neurons

Journal of Extracellular Vesicles, Год журнала: 2025, Номер 14(6)

Опубликована: Май 29, 2025

ABSTRACT Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects subcellular localisation of exosome precursor intraluminal (ILVs), microRNA (miR) packaging into ILVs vivo spreading neuronal EVs. By selectively labelling exosomes (but not plasma membrane‐derived MVs) with GFP‐tagged human CD63 (hCD63‐GFP) cortical neurons, we found glutamate stimulation significantly redistributes hCD63‐GFP + ILVs, especially decreasing its co‐localisation multi‐vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, only modestly alters miR profiles based on small RNA sequencing. Subsequent DREADD activation leads to more widespread area f/+ mice, consistently supporting stimulatory effect secretion spreading. Moreover, situ from specialised HB9 DAT neurons were also illustrated Taken together, our results demonstrated activity stimulates vitro vivo, but cargo exosomes.

Язык: Английский

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