High Frequency Oscillations (>250Hz) Outnumber Interictal Spikes in Preclinical Studies of Alzheimer’s Disease DOI Open Access
Christos Panagiotis Lisgaras, Helen E. Scharfman

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

ABSTRACT Interictal spikes (IIS) and seizures are well-documented in Alzheimer’s disease (AD). IIS typically outnumber seizures, supporting their role as a prominent EEG biomarker AD. In preclinical models, we showed that high frequency oscillations (HFOs>250Hz) also occur, but it is currently unknown how HFOs compare to IIS. Therefore, asked whether the incidence of differed if they differentially affected by behavioral state. We used three mouse lines simulate aspects AD: Tg2576, presenilin 2 knockout, Ts65Dn mice. recorded quantified hippocampus during wakefulness, slow-wave sleep, rapid eye movement sleep. all lines, were more frequent than High numbers correlated with fewer IIS, suggesting for first time possible competing dynamics among them Notably, occurred states summary, most abundant abnormality when compared states, better These findings pertained which important because different show may inhibit SHORT SUMMARY common occur earlier stages. comparison between lacking. Here 3 AD features local field potential recordings quantify HFOs. found outnumbered total inversely abnormality, this was generalizable across types

Language: Английский

Neuronal apoE4 induces early hyperexcitability in select populations of hippocampal neurons by altering Nell2 expression DOI Open Access
Dennis R. Tabuena, Sung-Soo Jang, Brian P. Grone

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 29, 2023

ABSTRACT The full impact of apolipoprotein E4 (APOE4), the strongest genetic risk factor for Alzheimer’s disease (AD), on neuronal and network function remains unclear. We found hippocampal region-specific hyperexcitability in young APOE4 knock-in (E4-KI) mice which predicted cognitive deficits at old age. Network E4-KI was mediated by subpopulations smaller hyperexcitable neurons that were eliminated selective removal APOE4. Aged exhibited granule cells, a progressive inhibitory deficit, E/I imbalance dentate gyrus, exacerbating hyperexcitability. Single-nucleus RNA-sequencing revealed cell type-specific age-dependent transcriptomic changes, including Nell2 overexpression mice. Reducing expression specific types with CRISPRi rescued their abnormal excitability phenotypes, implicating as cause APOE4-induced These findings highlight early electrophysiological alterations underlying dysfunction its contribution to AD pathogenesis aging.

Language: Английский

Citations

4
Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease DOI Creative Commons
Elissavet Chartampila, Karim S. Elayouby, Paige Leary

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 2, 2024

Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, the effects of MCS on neuronal hyperexcitability AD are unknown. We investigated a well-established mouse model with hyperexcitability, Tg2576 mouse. The most common type mice generalized EEG spikes (interictal [IIS]). IIS also other models and occur patients. In models, is reflected by elevated expression transcription factor ∆FosB granule cells (GCs) dentate gyrus (DG), which principal cell type. Therefore, we studied ΔFosB GCs. marker NeuN within hilar neurons DG because reduced protein sign oxidative stress or pathology. This potentially important regulate GC excitability. breeding pairs received diet relatively low, intermediate, high concentration choline. After weaning, all intermediate diet. offspring fed diet, frequency declined, was reduced, restored. Using novel object location task, spatial memory improved. contrast, exposed to low had several adverse effects, such as increased mortality. They weakest immunoreactivity greatest expression. their surprising. results provide new evidence that early life can improve outcomes AD, have mixed effects. first study showing dietary neurons, ΔFosB, an animal AD.

Language: Английский

Citations

1
Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease DOI Open Access
Elissavet Chartampila, Karim S. Elayouby, Paige Leary

et al.

Published: May 15, 2024

Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, effects of MCS on neuronal hyperexcitability AD are unknown. We investigated a well-established mouse model with hyperexcitability, the Tg2576 mouse. The most common type mice, and many other models patients, generalized EEG spikes (interictal spikes; IIS). Hyperexcitability is also reflected by elevated expression transcription factor ΔFosB granule cells (GCs) dentate gyrus (DG), which principal cell type. studied hilus DG because hilar neurons regulate GC excitability. found reduced marker NeuN within studies have shown sign oxidative stress or pathology.Tg2576 breeding pairs received diet relatively low, intermediate high concentration choline. After weaning, all mice diet. In offspring fed diet, IIS frequency declined, was reduced, restored. Spatial memory improved using novel object location task. contrast, exposed to low had several adverse effects, such as increased mortality. They weakest immunoreactivity greatest ΔFosB. their surprising. results provide new evidence that early life can improve outcomes AD, mixed effects. This first study showing dietary neurons, spatial an animal AD.

Language: Английский

Citations

1
Alzheimer’s disease and epilepsy: Research hotspots for comorbidity in the era of global aging DOI
Xu Zhou, Yang Liu,

Zhengjuan Wu

et al.

Epilepsy & Behavior, Journal Year: 2024, Volume and Issue: 157, P. 109849 - 109849

Published: May 30, 2024

Language: Английский

Citations

0
Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease DOI Open Access
Elissavet Chartampila, Karim S. Elayouby, Paige Leary

et al.

Published: June 5, 2024

Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, effects of MCS on neuronal hyperexcitability AD are unknown. We investigated a well-established mouse model with hyperexcitability, the Tg2576 mouse. The most common type mice generalized EEG spikes (interictal spikes; IIS). IIS also other models and occur patients. Im models, is reflected by elevated expression transcription factor ΔFosB granule cells (GCs) dentate gyrus (DG), which principal cell type. Therefore we studied GCs. marker NeuN within hilar neurons DG because studies have reduced protein sign oxidative stress or pathology. This potentially important regulate GC excitability.Tg2576 breeding pairs received diet relatively low, intermediate high concentration choline. After weaning, all diet. In offspring fed diet, frequency declined, was reduced, restored. Using novel object location task, spatial memory improved. contrast, exposed to low had several adverse effects, such as increased mortality. They weakest immunoreactivity greatest expression. their surprising. results provide new evidence that early life can improve outcomes AD, mixed effects. first study showing dietary neurons, an animal AD.

Language: Английский

Citations

0
The role of the basal forebrain in the pathogenesis of Alzheimer’s disease DOI
Valentina Kitchigina, I. Yu. Popova, Liubov Shubina

et al.

Журнал высшей нервной деятельности им И П Павлова, Journal Year: 2024, Volume and Issue: 74(5), P. 538 - 564

Published: Nov. 27, 2024

Language: Английский

Citations

0
Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease DOI Creative Commons
Elissavet Chartampila, Karim S. Elayouby, Paige Leary

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 12, 2023

ABSTRACT Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, effects of MCS on neuronal hyperexcitability AD are unknown. We investigated a well-established mouse model with hyperexcitability, the Tg2576 mouse. The most common type mice generalized EEG spikes (interictal spikes; IIS). IIS also other models and occur patients. Im models, is reflected by elevated expression transcription factor ΔFosB granule cells (GCs) dentate gyrus (DG), which principal cell type. Therefore we studied GCs. marker NeuN within hilar neurons DG because studies have reduced protein sign oxidative stress or pathology. This potentially important regulate GC excitability. breeding pairs received diet relatively low, intermediate high concentration choline. After weaning, all diet. In offspring fed diet, frequency declined, was reduced, restored. Using novel object location task, spatial memory improved. contrast, exposed to low had several adverse effects, such as increased mortality. They weakest immunoreactivity greatest expression. their surprising. results provide new evidence that early life can improve outcomes AD, mixed effects. first study showing dietary neurons, an animal AD.

Language: Английский

Citations

1
High Frequency Oscillations (>250Hz) Outnumber Interictal Spikes in Preclinical Studies of Alzheimer’s Disease DOI Open Access
Christos Panagiotis Lisgaras, Helen E. Scharfman

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

ABSTRACT Interictal spikes (IIS) and seizures are well-documented in Alzheimer’s disease (AD). IIS typically outnumber seizures, supporting their role as a prominent EEG biomarker AD. In preclinical models, we showed that high frequency oscillations (HFOs>250Hz) also occur, but it is currently unknown how HFOs compare to IIS. Therefore, asked whether the incidence of differed if they differentially affected by behavioral state. We used three mouse lines simulate aspects AD: Tg2576, presenilin 2 knockout, Ts65Dn mice. recorded quantified hippocampus during wakefulness, slow-wave sleep, rapid eye movement sleep. all lines, were more frequent than High numbers correlated with fewer IIS, suggesting for first time possible competing dynamics among them Notably, occurred states summary, most abundant abnormality when compared states, better These findings pertained which important because different show may inhibit SHORT SUMMARY common occur earlier stages. comparison between lacking. Here 3 AD features local field potential recordings quantify HFOs. found outnumbered total inversely abnormality, this was generalizable across types

Language: Английский

Citations

0