Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer’s Disease

Jeong, Won-Hyeong; Kim, Wang-In; Lee, Jinwon; Park, Hyeng-Kyu; Song, Min-Keun; Choi, In-Sung; Han, Jae‐Young

doi:10.3390/brainsci11111532

Cited by 19 publications

(21 citation statements)

References 49 publications

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“…Neurophysiopathological measures were also collected in various studies. A commonly used outcome is the power spectral analysis of rs-EEG, due to the available evidence for progressive reduction in beta, alpha, and gamma, in favor of higher theta and delta activity in dementia (Jafari et al, 2020;Jeong et al, 2021). The high-to-low-frequency ratio is significantly decreased in clinically diagnosed AD patients compared to healthy individuals, with MCI patients remaining in between (Moretti et al, 2011;Musaeus et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…These findings have led to preclinical human studies using non-invasive brain stimulation (NIBS), and particularly transcranial Alternating Current Stimulation (tACS), a neuromodulation technique that applies a lowintensity sinusoidal electrical current to the brain through surface electrodes placed over the scalp (Wischnewsk et al, 2022;Gonzalez-Perez et al, 2019). This approach allows the entrainment of endogenous cortical oscillations in a frequency-and phase-specific manner by modulating the membrane potentials (Elyamany et al, 2021;Jeong et al, 2021). Gamma-tACS (γ-tACS) is a suitable approach to replicate, in humans, the promising effects seen in murine models of AD (McDermott et al, 2018;Menardi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

et al. 2023

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Despite the numerous pharmacological interventions targeting dementia, no disease-modifying therapy is available, and the prognosis remains unfavorable. A promising perspective involves tackling high-frequency gamma-band (> 30 Hz) oscillations involved in hippocampal-mediated memory processes, which are impaired from the early stages of typical Alzheimer’s Disease (AD). Particularly, the positive effects of gamma-band entrainment on mouse models of AD have prompted researchers to translate such findings into humans using transcranial alternating current stimulation (tACS), a methodology that allows the entrainment of endogenous cortical oscillations in a frequency-specific manner. This systematic review examines the state-of-the-art on the use of gamma-tACS in Mild Cognitive Impairment (MCI) and dementia patients to shed light on its feasibility, therapeutic impact, and clinical effectiveness. A systematic search from two databases yielded 499 records resulting in 10 included studies and a total of 273 patients. The results were arranged in single-session and multi-session protocols. Most of the studies demonstrated cognitive improvement following gamma-tACS, and some studies showed promising effects of gamma-tACS on neuropathological markers, suggesting the feasibility of gamma-tACS in these patients anyhow far from the strong evidence available for mouse models. Nonetheless, the small number of studies and their wide variability in terms of aims, parameters, and measures, make it difficult to draw firm conclusions. We discuss results and methodological limitations of the studies, proposing possible solutions and future avenues to improve research on the effects of gamma-tACS on dementia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

et al. 2023

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“…In tau overexpressing neurofibrillary tangle-bearing mice 40 Hz light flicker improved synaptic integrity markers such as brain-derived neurotrophic factor (BDNF) and synaptophysin (Adaikkan et al, 2019;Park et al, 2020). On the other hand, Jeong et al reported that 40 Hz transcranial electrical stimulation reversed impaired hippocampal LTP in the absence of changes in BDNF expression in young 5xFAD mice in the absence of tau deposition (Jeong et al, 2021). The attempts to restore/influence gamma power in AD are still at an investigational stage as no changes in AD biomarkers in humans after such treatment have been reported to date (Manippa et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease

Yin

Ondrejčák

et al. 2023

Preprint

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Non-invasive sensory stimulation in the range of the brain’s gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). Here we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily sessions of 40 Hz sensory stimulation fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.

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“…Preclinical translational animal studies play a major role in neuroscience research to understand the roles of neuropeptides, neurohormones, and endogenous biomolecules in the normal function of human life such as cognition, emotion, and social interaction, and in pathological alterations developing into neurological and psychiatric disorders [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97]. Various bioactive molecules are synthesized in the Try-KYN metabolic system.…”

Section: Discussionmentioning

confidence: 99%

Memory Enhancement with Kynurenic Acid and its Mechanisms in Neurotransmission

Martos¹,

Tuka²,

Tanaka³

et al. 2022

Preprint

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Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.

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Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer’s Disease

Cited by 19 publications

References 49 publications

Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review

Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease

Memory Enhancement with Kynurenic Acid and its Mechanisms in Neurotransmission

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