Understanding the Molecular Impact of Physical Exercise on Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13576 - 13576

Published: Dec. 18, 2024

Alzheimer’s disease is one of the most common neurodegenerative diseases, characterized by a wide range neurological symptoms that begin with personality changes and psychiatric symptoms, progress to mild cognitive impairment, eventually lead dementia. Physical exercise part non-pharmacological treatments used in disease, as it has been shown delay process improving redox state brain tissue, providing anti-inflammatory effects or stimulating release brain-derived neurotrophic factor enhances structure performance. Here, we reviewed results obtained from studies conducted both animal models human subjects comprehend how physical interventions can exert molecular mechanisms underlying pathophysiological processes disease: amyloid β-peptide pathology, tau neuroglial changes, mitochondrial dysfunction, oxidative stress. seems have protective effect against since induce positive some biomarkers related disease. However, additional humans are necessary address current lack conclusive evidence.

Language: Английский

---

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(5), P. 2095 - 2116

Published: Nov. 12, 2022

Abstract Introduction Synaptic failure, a hallmark of Alzheimer's disease (AD), is correlated with reduced levels synaptic proteins. Though people Down syndrome (DS) are at markedly increased risk for AD (AD‐DS), few studies have addressed synapse dysfunction. Methods proteins were measured in the frontal cortex DS, AD‐DS, sporadic cases, and controls. The same examined Dp16 model DS. Results A common subset but not DS or case partial trisomy 21 lacking triplication APP gene. Pointing to compromised function, reductions AD‐DS SNARE complexes. In mice syntaxin 1A, SNAP25 complex recapitulated findings AD‐DS; impacted by both age App gene dose. Discussion phenotypes shared between point pathogenetic mechanisms.

Language: Английский

---

Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: June 26, 2023

Background Ketamine and psychedelics have abuse liability. They can also induce “transformative experiences” where individuals experience enhanced states of awareness. This awareness lead to changes in preexisting behavioral patterns which could be beneficial the treatment substance use disorders (SUDs). Preclinical clinical studies suggest that ketamine may alter markers associated with synaptic density, these underlie effects such as sensitization, conditioned place preference, drug self-administration, verbal memory performance. In this scoping review, we examined measured animals humans after exposure and/or psychedelics. Methods A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, Web Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9 ). Both vivo vitro were included. Studies included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, SV2A. Results Eighty-four included final analyses. Seventy-one treatment, nine psychedelics, four both. Psychedelics psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, ibogaine/noribogaine. Mixed findings regarding hippocampus prefrontal cortex (PFC) been reported when administered single dose under basal conditions. Similar mixed seen conditions used repeated administration ketamine. However, during stressful found counteracted stress-related reductions PFC. Repeated stress hippocampus. generally increased markers, but results more consistently positive for certain agents. Conclusion increase Heterogeneous relate methodological differences, agents (or different formulations same agent), sex, type markers. Future address seemingly by using meta-analytical approaches or study designs fully consider individual differences.

Language: Английский

---

Mild Motor Signs in Healthy Aging Are Associated with Lower Synaptic Density in the Brain

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(10), P. 1786 - 1794

Published: Aug. 13, 2023

Abstract Objective To investigate whether mild motor signs (MMS) in old age correlate with synaptic density the brain. Background Normal aging is associated a decline movement quality and quantity, commonly termed “mild parkinsonian signs” or more recently MMS. Whether MMS stem from global brain pathology within circuits remains unresolved. The vesicle glycoprotein 2A positron emission tomography (PET) ligand 11 C‐UCB‐J allows investigation of brain‐motor associations at level vivo. Method Fifty‐eight healthy older adults (≥50 years) were included two monocentric control cohorts. Brain magnetic resonance imaging PET data available 54 participants. binding was quantified by standardized uptake value ratio (SUVR) values grey matter (GM) volumes interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, frontal, parietal, temporal, occipital cortex. Multiple linear regression analyses performed Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score measuring as dependent variable mean SUVR each VOI independent age, Fazekas (white lesion [WML] load), cohort covariates. Results Participants (68 ± 7.5 years; 52% female) had an average MDS‐UPDRS 3.3 2.8. inversely density, independently WML load GM volume, occipital, temporal Cohen's f 2 showed moderate effect sizes for subcortical (range, 0.30–0.35), cortical (0.28–0.35) cerebellar VOIs (0.31). Conclusion are lower throughout © 2023 International Parkinson Society.

Language: Английский

---

Synaptic density affects clinical severity via network dysfunction in syndromes associated with frontotemporal lobar degeneration

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 20, 2023

Abstract There is extensive synaptic loss from frontotemporal lobar degeneration, in preclinical models and human vivo post mortem studies. Understanding the consequences of for network function important to support translational guide future therapeutic strategies. To examine this relationship, we recruited 55 participants with syndromes associated degeneration 24 healthy controls. We measured density positron emission tomography using radioligand [ 11 C]UCB-J, which binds presynaptic vesicle glycoprotein SV2A, neurite dispersion diffusion magnetic resonance imaging, task-free imaging functional connectivity. Synaptic patients was reduced connectivity beyond atrophy. Functional moderated relationship between clinical severity. Our findings confirm importance syndromes, resulting effect on behaviour as a abnormal

Language: Английский

---