Age-dependent disruption in hippocampal theta oscillation in amyloid-β overproducing transgenic mice

Scott, Liam; Feng, Jianlin; Kiss, Tamás; Needle, Elie; Atchison, Kevin; Kawabe, Thomas T.; Milici, Anthony J.; Hajós‐Korcsok, Éva; Riddell, David; Hajós, Mihály

doi:10.1016/j.neurobiolaging.2011.12.010

Cited by 72 publications

(84 citation statements)

References 39 publications

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“…This presumption is supported by the presence of only mature fibrillary plaques, without new inflammatory plaques, in the hippocampus of 24-month-old APP/PS1 mice. Similar to adult APP/PS1 mice, the deposition of Aβ plaques was mainly present in the molecular layer and stratum lacunosum moleculare, while being virtually absent in the pyramidal cell layer and the granule cell layer (Bas Orth et al 2005;Oksman et al 2006;Donkin et al 2010;Scott et al 2012;Xu et al 2012Xu et al , 2016. Furthermore, our previous and present results suggest that laminar heterogeneity and Aβ load is correlated with laminar variability in expression of APP secretases (Xu et al 2016).…”

Section: Discussionsupporting

confidence: 70%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/ PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

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Section: Discussionsupporting

confidence: 70%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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“…Although we have shown that pharmacological activation of α7 nAChRs leads to enhanced hippocampal theta oscillations, it was unknown if physiological activity of α7 nAChRs are contributing to elicited hippocampal theta oscillations. Similarly to previous findings obtained in anesthetized mice [47,58,63,67], stimulation of the nPO elicited regular theta oscillation in the hippocampal CA1 region both in α7 nAChR KO (n = 14) and WT (n = 14) adult mice with a current-dependent increase in peak frequency and power of theta. Comparing absolute power and peak frequency of elicited-theta oscillation between α7 nAChR KO and their age-matched WT controls, no significant difference was found in current-dependent increase in theta power or theta frequencies over the entire theta frequency range (Fig.…”

Section: Potential Intrinsic Roles Of α7 Nach Receptors In Hippocsupporting

confidence: 85%

“…Therefore, we tested PNU-282987 (Tocris Bioscience, Bristol, UK) in urethane anesthetized C57BL/6J mice at a dose of 3 mg/kg using our published protocols [67]. Similarly to our findings obtained in rats [43], PNU-282987 significantly increased theta power in urethane anesthetized mice as it is shown in Figure 3A and B, but gamma band power was not significantly influenced in the same set of animals.…”

Section: Effects Of α7 Nach Receptor Agonists On Npo-induced Hipsupporting

confidence: 55%

“…Furthermore, transgenic mice with impaired cognitive functions exhibit significantly reduced power of elicited hippocampal theta oscillations, including the NMDA receptors hypomorphic Grin1 mice and Aβ overproducing APP/PS1 mice [63,67]. In contrast, drugs used in clinical treatment of Alzheimer's disease patients, including acetylcholinesterase inhibitors and memantine, increase the power of elicited theta oscillation [27,58].…”

Section: Effects Of α7 Nach Receptor Agonists On Npo-induced Hipmentioning

confidence: 99%

“…Neuronal oscillations in α7 nAChR KO mice have not been previously tested in vivo; therefore, in our laboratory we recorded elicited hippocampal theta oscillations from 2-month old α7 nAChR KO and WT mice, using our published methods [47,67]. Although we have shown that pharmacological activation of α7 nAChRs leads to enhanced hippocampal theta oscillations, it was unknown if physiological activity of α7 nAChRs are contributing to elicited hippocampal theta oscillations.…”

Section: Potential Intrinsic Roles Of α7 Nach Receptors In Hippocmentioning

confidence: 99%

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Modulation of hippocampal neuronal network oscillations by α7 nACh receptors

Stoiljković

Kelley

Nagy

et al. 2015

Biochemical Pharmacology

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Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease

Benussi

Cantoni

Grassi

et al. 2022

Annals of Neurology

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Objective This study aimed to assess whether non‐invasive brain stimulation with transcranial alternating current stimulation at gamma‐frequency (γ‐tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD). Methods In this randomized, double‐blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre and post 60 minutes treatment with γ‐tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ‐tACS efficacy were evaluated. Results We observed a significant improvement in the Rey Auditory Verbal Learning (RAVL) test immediate recall (p < 0.001) and delayed recall scores (p < 0.001) after γ‐tACS but not after sham tACS. Face‐name associations scores improved with γ‐tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ‐tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ‐tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus. Interpretation Precuneus γ‐tACS, able to increase γ‐power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ‐tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022;92:322–334

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Age-dependent disruption in hippocampal theta oscillation in amyloid-β overproducing transgenic mice

Cited by 72 publications

References 39 publications

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Modulation of hippocampal neuronal network oscillations by α7 nACh receptors

Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease

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