The Dietary Sugars Intake: The Role In Alzheimer’s Disease Pathomechanism DOI Creative Commons

Rifka Wangiana Yulia Putri,

Dwi Pratika Anjarwati,

Damar Mashkhun Rizqi

et al.

Clinical and Research Journal in Internal Medicine, Journal Year: 2023, Volume and Issue: 4(1), P. 404 - 417

Published: May 25, 2023

Alzheimer’s disease is a common neurodegenerative that affect elderly and it became serious global burden for years. Despite many studies have been performed, an effective cure was still not be found. Therefore, necessary to only focus on curative methods but also preventive with modifiable risk factors underlying disease, example lifestyle metabolic as potential approach in prevention the future. The excessive dietary sugar intake has suggested factor of diseases such cognitive impairment disease. It may promote declines through some pathways induce alteration gut microbiomes, metabolism immune system. These abnormal processes evoke amyloid β plaque formation neurofibrillary tangles brain cells effect chronic inflammation. Chronic inflammation widely studied hallmark pathology. correlation between cognitive, specifically will summarized.

Language: Английский

Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimer's disease DOI Creative Commons
Michael A. Kelberman, Jacki M. Rorabaugh,

Claire R. Anderson

et al.

Neurobiology of Aging, Journal Year: 2023, Volume and Issue: 125, P. 98 - 108

Published: Feb. 1, 2023

Language: Английский

Citations

27
Causal relationship between dietary habits and Alzheimer's disease risk: a univariable and multivariable Mendelian randomization study DOI
Yi Huang, Mingyue Zhao, Hongbing Shen

et al.

Food & Function, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The objective of this study was to evaluate the causal link between dietary habits and Alzheimer's disease (AD), utilizing a two-sample Mendelian randomization approach.

Language: Английский

Citations

1
Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model DOI Creative Commons
Monica van den Berg, Daniëlle Toen, Marleen Verhoye

et al.

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 22, 2023

Alzheimer’s disease (AD) is a severe neurodegenerative disorder caused by the accumulation of toxic proteins, amyloid-beta (Aβ) and tau, which eventually leads to dementia. Disease-modifying therapies are still lacking, due incomplete insights into neuropathological mechanisms AD. Synaptic dysfunction known occur before cognitive symptoms become apparent recent studies have demonstrated that imbalanced synaptic signaling drives progression AD, suggesting early could be an interesting therapeutic target. results in altered oscillatory activity, can detected with electroencephalography electrophysiological recordings. However, majority these been performed at advanced stages when extensive damage already present. The current study aimed investigate if hippocampal activity pre-plaque rats received stereotactic surgery implant laminar electrode CA1 layer right hippocampus. Electrophysiological recordings during two consecutive days open field were 4–5-month-old TgF344-AD increased concentrations soluble Aβ species observed brain, absence Aβ-plaques. We decreased power high theta oscillations compared wild-type littermates. Sharp wave-ripple (SWR) analysis revealed SWR duration quiet wake rats. alterations properties fast suggestive neuronal hyperexcitability, as has presymptomatic In addition, strength theta-gamma coupling, important correlate memory encoding, was Theta-gamma phase amplitude coupling associated encoding execution functions. Studies mild impairment patients display strength, similar what described here. demonstrates network occurring AD provides prodromal aid detection stages.

Language: Английский

Citations

18
Obesity during preclinical Alzheimer's disease development exacerbates brain metabolic decline DOI
Thea Anderson, Sumeet K. Sharma, Michael A. Kelberman

et al.

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 168(5), P. 801 - 821

Published: June 30, 2023

Abstract Alzheimer's disease (AD) is the most common form of dementia. Obesity in middle age increases AD risk and severity, which alarming given that obesity prevalence peaks at rates are accelerating worldwide. Midlife, but not late‐life risk, suggesting this interaction specific to preclinical AD. pathology begins age, with accumulation amyloid beta (Aβ), hyperphosphorylated tau, metabolic decline, neuroinflammation occurring decades before cognitive symptoms appear. We used a transcriptomic discovery approach young adult (6.5 months old) male female TgF344‐AD rats overexpress mutant human precursor protein presenilin‐1 wild‐type (WT) controls determine whether inducing high‐fat/high‐sugar “Western” diet during brain dysfunction dorsal hippocampus (dHC), region vulnerable effects early Analyses dHC gene expression data showed dysregulated mitochondrial neurotransmission pathways, up‐regulated genes involved cholesterol synthesis. Western amplified number were different between WT added pathways noradrenergic signaling, inhibition synthesis, decreased intracellular lipid transporters. Importantly, impaired dHC‐dependent spatial working memory rats, confirming dietary intervention accelerated decline. To examine later consequences transcriptional dysregulation, we measured monoamine levels older (13 both sexes after long‐term chow or consumption. Norepinephrine (NE) abundance was significantly NE turnover increased, attenuated AD‐induced turnover. Collectively, these findings indicate prodromal impairs memory, potentiates decline likely leading an overproduction cholesterol, interferes compensatory transmission. image

Language: Английский

Citations

16
The Neurotoxin DSP-4 Dysregulates the Locus Coeruleus-Norepinephrine System and Recapitulates Molecular and Behavioral Aspects of Prodromal Neurodegenerative Disease DOI Creative Commons

Alexa F. Iannitelli,

Michael A. Kelberman, Daniel J. Lustberg

et al.

eNeuro, Journal Year: 2022, Volume and Issue: 10(1), P. ENEURO.0483 - 22.2022

Published: Dec. 9, 2022

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) Parkinson's (PD), respectively. onset these pathologies coincides with loss fibers LC target regions emergence prodromal symptoms including sleep disturbances anxiety. Paradoxically, are indicative a hyperactivity phenotype, rather than predicted norepinephrine (NE) transmission following damage, suggesting engagement complex compensatory mechanisms. Because current therapeutic efforts targeting early disease, interest has grown, it critical to identify links between dysfunction. We employed LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which preferentially damages axons, model changes LC-NE system pertinent AD PD male female mice. DSP-4 (two doses 50 mg/kg, one week apart) induced axon degeneration, triggered neuroinflammation oxidative stress, reduced tissue NE levels. There was no cell death or firing, but transcriptomics revealed expression genes that define identity other relevant neurodegenerative disease. Despite dramatic fibers, turnover signaling were elevated terminal associated anxiogenic phenotypes multiple behavioral tests. These results represent comprehensive analysis how responds axon/terminal damage reminiscent at molecular, cellular, systems, levels, provides potential mechanisms underlying neuropsychiatric symptoms.

Language: Английский

Citations

23
Protective effects of polydatin amphiphilic chitosan nanocarriers against an aluminum chloride-induced model of Alzheimer’s disease in rats: relevance to its anti-inflammatory and antioxidant effects DOI Creative Commons

Seyede Nazanin Zarneshan,

Elham Arkan, Amir Kiani

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

0
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 DOI Creative Commons

Anett Futácsi,

Kitti Rusznák,

Gergely Szarka

et al.

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

Citations

0
Probiotic supplement as a promising strategy in early tau pathology prevention: Focusing on GSK-3β? DOI Creative Commons

Cassandra M. Flynn,

Qi Yuan

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

Published: March 22, 2023

Neurofibrillary tangles (NFT) is one of the hallmarks Alzheimer’s disease (AD). Recent research suggests that pretangle tau, soluble precursor NFT, an initiator for AD pathogenesis, thus targeting tau pathology may be a promising early intervention focus. The bidirectional communications between gut and brain play crucial role in health. compromised gut-brain axis involved various neurodegenerative diseases including AD. However, most on relationship microbiome have focused amyloid-β. In this mini review, we propose to target preclinical stages with microbiota interventions such as probiotic supplementation. We discuss importance starts decades before onset clinical symptoms, potential focusing regulation hyperphosphorylation. A particular focus GSK-3β, protein kinase at interface phosphorylation, diabetes mellitus.

Language: Английский

Citations

10
Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors DOI Creative Commons
Michael A. Kelberman, Ellen M. Rodberg, Ehsan Arabzadeh

et al.

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

Published: Oct. 16, 2024

Abstract The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution woven the LC into wide-ranging neural circuits that influence functions as broad autonomic systems, stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility activity inherently similar species, furthermore age, sex, brain state similarly species. degree to which homogenous these factors, however, never assessed due small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) show diversity both intrinsic extrinsic factors such sex state. We use negative binomial regression model compare male monkeys, rats mice sexes were recorded states slices ex vivo or under different anesthetics during wakefulness in . differed complex interactions became more active aging, independent sex. Finally, contrast foundational principle all species express two distinct firing modes (“tonic” “phasic”), discovered great within spontaneous patterns. Different associated with higher incidence some modes. conclude evolutionarily-ancient not conserved. Inherent differences age species-sex-brain have implications for understanding role species-specific naturalistic behavior, well psychiatric disorders, cardiovascular disease, immunology, metabolic disorders.

Language: Английский

Citations

3
Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus DOI Creative Commons

Alexa F. Iannitelli,

Leslie Hassenein,

Bernard Mulvey

et al.

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

Published: March 10, 2023

Abstract The locus coeruleus (LC), the major source of norepinephrine (NE) in brain, is an early site pathology both Alzheimer’s disease (AD) and Parkinson’s (PD), it undergoes catastrophic degeneration later disorders. Dysregulation LC thought to contribute prodromal symptoms AD PD such as anxiety sleep disturbances, while frank LC-NE loss promotes cognitive decline. However, mechanisms responsible for its selective vulnerability are unknown. among only structures brain that produces appreciable amounts neuromelanin (NM), a dark cytoplasmic pigment. It has been proposed NM initially plays protective role by sequestering toxic catecholamine metabolites heavy metals, but may become harmful during aging overwhelms cellular machinery released neurodegeneration. Rodents do not naturally produce NM, limiting study causal relationships between pathology. Adapting viral-mediated approach expression human tyrosinase, enzyme peripheral melanin production, we successfully promoted pigmentation mouse neurons recapitulates key ultrastructural features endogenous found primates. Pigment results neuron hyperactivity, reduced tissue NE levels, transcriptional changes, novelty-induced phenotypes 1-week post-injection. By 6-10 weeks, accumulation associated with severe neurodegeneration microglial engulfment pigment granules, anxiety-like behavior abated. These reminiscent dysfunction cell death PD, validating this model studying consequences relates neurodegenerative disease.

Language: Английский

Citations

8