The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 21, 2024

Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply active neurons in the brain. NVC damage can lead chronic impairment of neuronal function. Diabetes characterized by high sugar and considered risk factor for cognitive impairment. In this review, we provide fMRI evidence diabetic patients with decline. Combined exploration major mechanisms signaling pathways NVC, discuss effects hyperglycemia on cellular structure signaling, including key receptors, ion channels, intercellular connections. Studying these diabetes-related changes cell will help us understand underlying causes behind diabetes-induced early decline, ultimately helping identify most effective drug targets treatment.

Language: Английский

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Distinct Disruptions in CA1 and CA3 Place Cell Function in Alzheimer’s Disease Mice

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111631 - 111631

Published: Jan. 10, 2025

The hippocampus, a critical brain structure for spatial learning and memory, is susceptible to neurodegenerative disorders such as Alzheimer's disease (AD). Utilizing APPswe/PSEN1dE9 (APP/PS1) mice, we investigated neurophysiological mechanisms underlying AD-associated cognitive impairments by assessing place cell activities in CA1 CA3 hippocampal subregions, which have distinct yet complementary computational roles. Analyses revealed significant deterioration representation capabilities of APP/PS1 relative wild-type (WT) mice. Specifically, cells exhibited reduction coherence information, while displayed field size. Place both subregions showed disruption stability burst firing properties. Furthermore, theta rhythm was significantly attenuated These findings elucidate that physiological perturbations cells, coupled with disrupted rhythmicity CA1, potentially orchestrate the impairment hippocampal-dependent memory AD pathogenesis.

Language: Английский

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Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 12, 2025

Background Animal models of Alzheimer’s disease (AD) are essential tools for investigating pathophysiology and conducting preclinical drug testing. In this study, we examined neuronal glial alterations in the hippocampus medial prefrontal cortex (mPFC) young TgF344-AD rats correlated these changes with cognitive decline amyloid-β plaque load. Methods We compared non-transgenic littermate aged 7–8 months age. systematically quantified β-amyloid plaques, astrocytes, microglia, four different subtypes GABAergic interneurons (calretinin-, cholecystokinin-, parvalbumin-, somatostatin-positive neurons), newly generated neurons hippocampus. Spatial learning memory were assessed using Barnes maze test. Results Young had a large number amyloid plaques both mPFC, together pronounced increase microglial cell numbers. Astrocytic activation was significant mPFC. Cholecystokinin-positive numbers decreased transgenic rats, but calretinin-, not altered. Adult neurogenesis affected by genotype. spatial impairments, deficit did correlate or cellular brain. hippocampus, negatively cholecystokinin-positive neuron astrocytes. Conclusion Pronounced neuropathological found mPFC including loss hippocampal interneurons. Some load, impairment.

Language: Английский

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Insights From TgF344-AD, a Double Transgenic Rat Model in Alzheimer’s Disease Research

Physiological Research, Journal Year: 2025, Volume and Issue: 1/2025, P. 1 - 17

Published: March 10, 2025

Alzheimer's disease (AD), a leading cause of dementia worldwide, is multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused various genetic environmental factors. Numerous transgenic rodent models have been developed to understand pathology development progression. The TgF344-AD rat model double that carries two human mutations: APP the Swedish mutation PSEN-1 Δ exon 9 mutations. This exhibits complete repertoire in an age-dependent manner. review summarizes multidisciplinary research insights gained from studying rats context pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, altered sleep architecture; behavioral studies highlighting impaired memory; alterations excitatory-inhibitory systems; molecular physiological changes emphasizing their age-related effects. Additionally, impact interventions studied compiled, underscoring role bridging gaps understanding pathogenesis. offers significant potential identifying biomarkers for early detection therapeutic interventions, providing robust platform advancing translational research.

Language: Английский

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Unleashing the potential: 40 Hz multisensory stimulation therapy for cognitive impairment

Journal of Central Nervous System Disease, Journal Year: 2025, Volume and Issue: 17

Published: March 1, 2025

Cognitive impairment encompasses a spectrum of disorders marked by acquired deficits in cognitive function, potentially leading to diminished daily functioning and work capacity, often accompanied psychiatric behavioral disturbances. Alzheimer's disease (AD) Post-stroke (PSCI) are significant causes decline. With the global population getting older, AD PSCI becoming major health concerns, underscoring critical necessity for successful treatment options. In recent years, various non-invasive biophysical stimulation techniques, including ultrasound, light, electric, magnetic stimulation, have been developed central nervous system diseases. Preliminary clinical studies demonstrated feasibility safety these techniques. This review discuss impact 40 Hz multisensory on cerebral outcomes, progression both animal models individuals exhibiting deficits, such as PSCI. Furthermore, it summarizes potential neural pathways involved this therapeutic modality synthesizing evidence from variety within field. Subsequently, evaluates existing constraints technique underscores advantages therapy with goal enhancing management care

Language: Английский

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Transcranial magneto-acoustic stimulation improves spatial memory and modulates hippocampal neural oscillations in a mouse model of Alzheimer's disease

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 7, 2024

Introduction In our study, we applied transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound within static magnetic field, in the APP/PS1 mouse model of Alzheimer's disease (AD) to explore feasibility TMAS improving AD related spatial memory deficits and abnormal neural oscillations. Methods The mice treated with once daily for 21 days. We recorded local field potential signals hippocampal CA1 region after treatment in-vivo electrophysiology evaluated rehabilitative effect sharp-wave ripple (SWR), gamma oscillations during SWRs, phase-amplitude coupling (PAC). function was examined by Morris water maze (MWM) task. Results found that improved performance MWM cognitive functions compared group. Furthermore, results implied alleviated abnormalities increased slow power promoted theta-slow coupling. These findings suggest could have positive influence through modulation Discussion This work emphasizes serve as non-invasive method rehabilitation promote application more neurological brain aging diseases future.

Language: Английский

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Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer’s disease using hippocampal 40 Hz stimulation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

In preclinical Alzheimer's disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for consolidation) potential mechanism AD. previously found deficits HPC-cortical coordination coinciding with VM the next day. Some forms of 40 Hz stimulation seem clear AD pathology mice, improve functional connectivity patients. Thus, we implanted recording array targeting parietal cortex (PC) HPC assess HPC-PC coordination, an optical fiber or sham optogenetic 3xTg/PV

Language: Английский

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Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism

Brain Research Bulletin, Journal Year: 2023, Volume and Issue: 202, P. 110750 - 110750

Published: Aug. 23, 2023

The deposition of amyloid β peptide (Aβ) is one the main pathological features AD. much-talked sensory gamma entrainment may be a new treatment for Aβ load. Here we reviewed generation and clearance pathways Aβ, aberrant oscillation in AD, therapeutic effect on In addition, discuss these results based stimulus parameters possible potential mechanisms. This provides support targeting to improve

Language: Английский

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Linking Social Cognition, Parvalbumin Interneurons, and Oxytocin in Alzheimer’s Disease: An Update

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 96(3), P. 861 - 875

Published: Nov. 17, 2023

Finding a cure for Alzheimer’s disease (AD) has been notoriously challenging many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing progression in earliest stages. A better understanding of underlying mechanisms at beginning could aid early diagnosis including alleviating symptoms or down progression. Changes social cognition progressive parvalbumin (PV) interneuron dysfunction are among observable effects AD. Various AD rodent models mimic these alterations, but only narrow field study considered their mutual relationship. In this review, we discuss knowledge about PV emphasize importance memory. Next, propose oxytocin (OT) as potent modulator interneurons promising treatment managing some symptoms. We further supporting evidence its beneficial AD-related pathology. Clinical trials have employed use OT various neuropsychiatric diseases with results, little known prospective impacts On other hand, modulatory specific structures local circuits need to be clarified future studies. This review highlights connection between impairment stages considers therapeutic agent addressing deficits.

Language: Английский

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Linking temporal coordination of hippocampal activity to memory function

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 31, 2023

Oscillations in neural activity are widespread throughout the brain and can be observed at population level through local field potential. These rhythmic patterns associated with cycles of excitability thought to coordinate networks neurons, turn facilitating effective communication both within circuits across regions. In hippocampus, theta rhythms (4–12 Hz) could contribute several key physiological mechanisms including long-range synchrony, plasticity, behavioral scale, support memory encoding retrieval. While neurons hippocampus appear temporally coordinated by oscillations, they also tend fire sequences that developmentally preconfigured. Although loss rhythmicity impairs memory, these spatiotemporal representations persist conditions altered hippocampal oscillations. The focus this review is disentangle relative contribution oscillations from single-neuron learning memory. We first cellular, anatomical, underlying generation maintenance how function. propose candidate hypotheses for septohippocampal function while not contributing directly sequences. particular, we explore integration upstream signals form future decisions, relevance such downstream regions, as well setting stage timescale synaptic plasticity. Finally, leverage stimulation-based treatment Alzheimer's disease an opportunity assess sufficiency

Language: Английский

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