Chronic administration of non-constitutive proteasome inhibitor modulates plasticity in hippocampus following tetanic stimulation, but not short theta-burst stimulation.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA952533 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24079374.fastq.gz | Fastqsanger.gz | |||
| SRR24079375.fastq.gz | Fastqsanger.gz | |||
| SRR24079376.fastq.gz | Fastqsanger.gz | |||
| SRR24079377.fastq.gz | Fastqsanger.gz | |||
| SRR24079378.fastq.gz | Fastqsanger.gz |
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Project description:Proteasomes degrade most intracellular proteins. Several different forms of proteasomes are known. Proteasome inhibitors targeting different proteasome forms are used in clinical practice and were shown to modulate long-term potentiation (LTP) in hippocampal slices of untreated animals. Here we studied the effect of chronic administration of non-constitutive proteasome inhibitor ONX-0914 on the LTP induced by two different protocols: tetanic stimulation and theta-burst stimulation (TBS). Excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from control animals and animals treated with DMSO or ONX-0914 were compared. The TBS stimulation did not change LTP kinetics in hippocampal slices, however chronic administration of ONX-0914 led to the decrease in fEPSP slopes after tetanic stimulation. Observed effects correlated with differential expression of genes involved in synaptic plasticity, glutaminergic synapse and synaptic signaling. Obtained results indicate that non-constitutive proteasomes are likely involved in the tetanus-evoked LTP but not the LTP occurring after TBS, supporting the relevance and complexity of the role of proteasomes in the synaptic plasticity.
2023-04-05 | GSE229000 | GEO
Project description:A significant population of chronic stroke patients urgently requires more effective therapies due to functional plateaus and limited intervention options. Intermittent theta-burst stimulation (iTBS) has been increasingly adopted in chronic-phase ischemic stroke management. However, the efficacy decreases over time. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy for chronic stroke management through multiple mechanisms. Whether combined MSC transplantation and iTBS confers superior synergistic efficacy warrants further investigation. In this study, human umbilical cord-derived MSCs were stereotactically injected into the penumbra of the brain parenchyma adjacent to infarct sites in cynomolgus monkeys with chronic-stage middle cerebral artery occlusion (MCAO)-induced ischemic stroke. iTBS commenced at 1 week post-transplantation (5 sessions/week until week 17). Behavioral tests, electrophysiological recordings, functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and plasma proteomic analysis were conducted longitudinally, with terminal histological and spatial proteomic analysis at week 17. The results demonstrated that combined MSC/iTBS therapy enhanced motor function, reduced cortical excitation thresholds, shortened motor-evoked potential (MEP) latency, increased neural activity intensity/synchronization, strengthened functional connectivity, and optimized motor cortex metabolism. In addition to the commonly attributed therapeutic mechanisms of MSCs and iTBS, the combined therapy additionally triggered neurogenesis and stem cell chemotaxis, which was potentially mediated by iTBS-enhanced CXCL12 secretion from MSCs. Therefore, MSC/iTBS combination therapy can effectively treat chronic stroke through multiple mechanisms, particularly involving the activation of endogenous neural stem cells (NSCs), representing a promising interdisciplinary treatment strategy.
2026-03-12 | PXD071582 | Pride
Project description:Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive tool used to study the brain and as an alternative treatment for neurological disorders. However, the molecular mechanisms affected in the brain regions at and beyond the stimulation site, and how this varies with different rTMS protocols in an aged brain remains unclear. Here we use a combination of bulk RNA-sequencing and spatial transcriptomics to map the molecular changes across a mouse brain in response to two commonly used rTMS protocols: intermittent (iTBS) and continuous theta burst stimulation (cTBS).
2025-09-01 | GSE274782 | GEO
Project description:Repetitive transcranial magnetic stimulation (rTMS) is a widely adopted non-invasive tool used to study the brain and as an alternative treatment for neurological disorders. However, the molecular mechanisms affected in the brain regions at and beyond the stimulation site, and how this varies with different rTMS protocols in an aged brain remains unclear. Here we use a combination of bulk RNA-sequencing and spatial transcriptomics to map the molecular changes across a mouse brain in response to two commonly used rTMS protocols: intermittent (iTBS) and continuous theta burst stimulation (cTBS).
2025-09-01 | GSE274580 | GEO
Project description:Guillardia theta nucleomorph genome sequencing
| PRJNA27847 | ENA
Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).
| S-EPMC9433314 | biostudies-literature
Project description:BackgroundBrain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.ObjectiveOur study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture.MethodsWe recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity.ResultsWe found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain.ConclusionsBy demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks.
| S-EPMC9161680 | biostudies-literature
Project description: Not available
| S-EPMC7906022 | biostudies-literature
Project description:Theta-burst stimulation (TBS), a patterned brain stimulation technique that mimics rhythmic bursts of 3-8 Hz endogenous brain rhythms, has emerged as a promising therapeutic approach for treating a wide range of brain disorders, though the neural mechanism of TBS action remains poorly understood. We investigated the neural effects of TBS using intracranial EEG (iEEG) in 10 pre-surgical epilepsy participants undergoing intracranial monitoring. Here we show that individual bursts of direct electrical TBS at 29 frontal and temporal sites evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic local field potential voltage changes over the course of stimulation presentations, including either increasing or decreasing responses, suggestive of short-term plasticity. Stronger stimulation augmented the mean TBS response amplitude and spread with more recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific with stronger TBS responses observed in regions with strong baseline stimulation effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, we could use these measures to predict stable and varying (e.g. short-term plasticity) TBS response locations. Future work may integrate pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks.
| S-EPMC11324911 | biostudies-literature