scholarly journals Age-Related Memory Impairment Is Associated with Increased zif268 Protein Accumulation and Decreased Rpt6 Phosphorylation

2020 ◽  
Vol 21 (15) ◽  
pp. 5352
Author(s):  
Sydney Trask ◽  
Brooke N. Dulka ◽  
Fred J. Helmstetter
Keyword(s):  
Cognitive Decline ◽  
Brain Regions ◽  
Regulatory Subunit ◽  
Protein Accumulation ◽  
Memory Retention ◽  
Protein Levels ◽  
Trace Fear Conditioning ◽  
Age Related ◽  
Old Rats ◽  
Trace Fear

Aging is associated with cognitive decline, including impairments in the ability to accurately form and recall memories. Some behavioral and brain changes associated with aging are evident as early as middle age, making the understanding of associated neurobiological mechanisms essential to aid in efforts aimed at slowing cognitive decline throughout the lifespan. Here, we found that both 15-month-old and 22-month-old rats showed impaired memory recall following trace fear conditioning. This behavioral deficit was accompanied by increased zif268 protein accumulation relative to 3-month-old animals in the medial prefrontal cortex, the dorsal and ventral hippocampi, the anterior and posterior retrosplenial cortices, the lateral amygdala, and the ventrolateral periaqueductal gray. Elevated zif268 protein levels corresponded with decreases in phosphorylation of the Rpt6 proteasome regulatory subunit, which is indicative of decreased engagement of activity-driven protein degradation. Together, these results identify several brain regions differentially impacted by aging and suggest that the accumulation of proteins associated with memory retrieval, through reduced proteolytic activity, is associated with age-related impairments in memory retention.

scholarly journals Age-related memory deficits are associated with changes in protein degradation in brain regions critical for trace fear conditioning

2020 ◽  
Vol 91 ◽  
pp. 160-166 ◽  
Author(s):  
Brooke N. Dulka ◽  
Shane E. Pullins ◽  
Patrick K. Cullen ◽  
James R. Moyer ◽  
Fred J. Helmstetter
Keyword(s):  
Protein Degradation ◽  
Fear Conditioning ◽  
Memory Deficits ◽  
Brain Regions ◽  
Trace Fear Conditioning ◽  
Age Related ◽  
Trace Fear

Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

2018 ◽  
Vol 18 (5-6) ◽  
pp. 233-238
Author(s):  
Frederic Sampedro ◽  
Juan Marín-Lahoz ◽  
Saul Martínez-Horta ◽  
Javier Pagonabarraga ◽  
Jaime Kulisevsky
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Decline ◽  
De Novo ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Csf Biomarkers ◽  
Gene Encoding ◽  
Cortical Thinning ◽  
Age Related

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.

scholarly journals Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations Under Maternal High-Fat Diet Intake: Multigenerational Epigenetic Inheritance.

2020 ◽  
Author(s):  
Vanesa Izquierdo ◽  
Verónica Palomera-Ávalos ◽  
Mercè Pallàs ◽  
Christian Griñán-Ferré
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
High Fat Diet ◽  
Epigenetic Inheritance ◽  
Adult Offspring ◽  
High Fat ◽  
Molecular Alterations ◽  
Protein Levels ◽  
Age Related ◽  
Inflammatory Profile

Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

scholarly journals Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein–induced Inflammation through a Vagomimetic Action in Mice

2018 ◽  
Vol 128 (5) ◽  
pp. 921-931 ◽  
Author(s):  
Jun Hu ◽  
Susana Vacas ◽  
Xiaomei Feng ◽  
David Lutrin ◽  
Yosuke Uchida ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Fear Conditioning ◽  
Nicotinic Acetylcholine Receptors ◽  
Surgical Trauma ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Trace Fear Conditioning ◽  
Molecular Pattern ◽  
Molecular Group ◽  
Trace Fear

Abstract Background Inflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern–induced cognitive decline. Methods Cognitive decline (assessed by trace fear conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by proinflammatory cytokines. Results Damage-associated molecular pattern–induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear conditioning: 58.77 ± 8.69% vs. 41.45 ± 7.64%, P < 0.0001; plasma interleukin [IL]-1β: 7.0 ± 2.2 pg/ml vs. 49.8 ± 6.0 pg/ml, P < 0.0001; plasma IL-6: 3.2 ± 1.6 pg/ml vs. 19.5 ± 1.7 pg/ml, P < 0.0001; hippocampal IL-1β: 4.1 ± 3.0 pg/mg vs. 41.6 ± 8.0 pg/mg, P < 0.0001; hippocampal IL-6: 3.4 ± 1.3 pg/mg vs. 16.2 ± 2.7 pg/mg, P < 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α7 nicotinic acetylcholine receptors but not by α2 adrenoceptor blockade. Netrin-1, the orchestrator of inflammation–resolution, was upregulated (fold-change) by dexmedetomidine (lung: 1.5 ± 0.1 vs. 0.7 ± 0.1, P < 0.0001; spleen: 1.5 ± 0.2 vs. 0.6 ± 0.2, P < 0.0001), resulting in upregulation of proresolving (lipoxin-A4: 1.7 ± 0.2 vs. 0.9 ± 0.2, P < 0.0001) and downregulation of proinflammatory (leukotriene-B4: 1.0 ± 0.2 vs. 3.0 ± 0.3, P < 0.0001) humoral mediators that was prevented by α7 nicotinic acetylcholine receptor blockade. Conclusions Dexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways, thereby preventing damage-associated molecular pattern–mediated cognitive decline.

scholarly journals Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

2009 ◽  
Vol 297 (3) ◽  
pp. H1087-H1095 ◽  
Author(s):  
Lori S. Kang ◽  
Rafael A. Reyes ◽  
Judy M. Muller-Delp
Keyword(s):  
Superoxide Dismutase ◽  
Hydroxyl Radical ◽  
Immunoblot Analysis ◽  
Radical Formation ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Age Related ◽  
Old Rats ◽  
Coronary Arterioles ◽  
Reduced Flow

Aging contributes significantly to the development of cardiovascular disease and is associated with elevated production of reactive oxygen species (ROS). The beneficial effects of nitric oxide (NO)-mediated vasodilation are quickly abolished in the presence of ROS, and this effect may be augmented with aging. We previously demonstrated an age-induced impairment of flow-induced dilation in rat coronary arterioles. Therefore, the purpose of this study was to determine the effects of O2− scavenging, as well as removal of H2O2, the byproduct of O2− scavenging, on flow-mediated dilation in coronary resistance arterioles of young (4 mo) and old (24 mo) male Fischer 344 rats. Flow increased NO and H2O2 production as evidenced by enhanced diaminofluorescein and dichlorodihydrofluorescein fluorescence, respectively, whereas aging reduced flow-induced NO and H2O2 production. Endothelium-dependent vasodilation was evaluated by increasing intraluminal flow (5–60 nl/s) before and after treatment with the superoxide dismutase mimetic Tempol (100 μM), the H2O2 scavenger catalase (100 U/ml), or Tempol plus catalase. Catalase reduced flow-induced dilation in both groups, whereas Tempol and Tempol plus catalase diminished vasodilation in young but not old rats. Tempol plus deferoxamine (100 μM), an inhibitor of hydroxyl radical formation, reversed Tempol-mediated impairment of flow-induced vasodilation in young rats and improved flow-induced vasodilation in old rats compared with control. Immunoblot analysis revealed increases in endogenous superoxide dismutase, catalase, and nitrotyrosine protein levels with aging. Collectively, these data indicate that NO- and H2O2-mediated flow-induced signaling decline with age in coronary arterioles and that elevated hydroxyl radical formation contributes to the age-related impairment of flow-induced vasodilation.

scholarly journals Green Tea Catechins Trigger Immediate-Early Genes in the Hippocampus and Prevent Cognitive Decline and Lifespan Shortening

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1484 ◽  
Author(s):  
Keiko Unno ◽  
Monira Pervin ◽  
Kyoko Taguchi ◽  
Tomokazu Konishi ◽  
Yoriyuki Nakamura
Keyword(s):  
Cognitive Decline ◽  
Green Tea ◽  
Brain Function ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Memory Retention ◽  
Tea Catechins ◽  
Early Genes ◽  
Green Tea Catechins ◽  
Age Related

Senescence-accelerated mouse prone 10 (SAMP10) mice, after ingesting green tea catechins (GT-catechin, 60 mg/kg), were found to have suppressed aging-related decline in brain function. The dose dependence of brain function on GT-catechin indicated that intake of 1 mg/kg or more suppressed cognitive decline and a shortened lifespan. Mice that ingested 1 mg/kg GT-catechin had the longest median survival, but the dose was less effective at suppressing cognitive decline. The optimal dose for improving memory acquisition was 60 mg/kg, and memory retention was higher in mice that ingested 30 mg/kg or more. To elucidate the mechanism by which cognitive decline is suppressed by GT-catechin, changes in gene expression in the hippocampus of SAMP10 mice one month after ingesting GT-catechin were analyzed. The results show that the expression of immediate-early genes such as nuclear receptor subfamily 4 (Nr4a), FBJ osteosarcoma oncogene (Fos), early growth response 1 (Egr1), neuronal PAS domain protein 4 (Npas4), and cysteine-rich protein 61 (Cyr61) was significantly increased. These results suggest that GT-catechin suppresses age-related cognitive decline via increased expression of immediate-early genes that are involved in long-term changes in plasticity of synapses and neuronal circuits.

scholarly journals Early-life blockade of NMDA receptors induces epigenetic abnormalities in the adult medial prefrontal cortex: possible involvement in memory impairment in trace fear conditioning

2019 ◽  
Vol 237 (1) ◽  
pp. 231-248 ◽  
Author(s):  
Joachim Latusz ◽  
Marzena Maćkowiak
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptors ◽  
Fear Conditioning ◽  
Medial Prefrontal Cortex ◽  
Memory Retrieval ◽  
Early Life ◽  
Histone H3 ◽  
Protein Levels ◽  
Trace Fear Conditioning ◽  
Trace Fear

Abstract Rationale Several findings indicate that early-life dysfunction of N-methyl-d-aspartate (NMDA) receptors might cause schizophrenia-like abnormalities in adulthood that might be induced by impairments in epigenetic regulation. Objectives In the present study, we investigated whether postnatal blockade of NMDA receptors (within the first 3 weeks of life) by the competitive antagonist CGP 37849 (CGP) might affect some epigenetic markers in the adult medial prefrontal cortex (mPFC). Methods Histone H3 phosphorylation at serine 10 (H3S10ph), histone H3 acetylation at lysine 9 or 14 (H3K9ac or H3K14ac, respectively), or expression of histone deacetylase (HDAC) 2, HDAC5, myocyte enhancer factor (MEF) 2D and activity-regulated cytoskeleton-associated protein (Arc) were analysed. Moreover, we also evaluated whether the deacetylase inhibitor sodium butyrate (SB; 1.2 mg/kg, ip) could prevent behavioural and neurochemical changes in the mPFC induced by CGP during memory retrieval in the trace fear conditioning paradigm. Results The results showed that CGP administration increased the number of H3S10ph nuclei but did not affect H3K9ac and H3K14ac or HDAC2 protein levels. However, CGP administration altered the HDAC5 mRNA and protein levels and increased the mRNA and protein levels of MEF2D. CGP also increased Arc mRNA, which was correlated with an increase in the amount of Arc DNA bound to MEF2D. SB given 2 h after training prevented impairment of the freezing response and disruption of epigenetic markers (H3S10ph, HDAC5, MEF2D) and Arc expression during memory retrieval induced by CGP administration. Conclusions The early-life blockade of NMDA receptors impairs some epigenetic regulatory processes in the mPFC that are involved in fear memory formation.

scholarly journals Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

2019 ◽  
Vol 20 (5) ◽  
pp. 1134 ◽  
Author(s):  
Vanesa Izquierdo ◽  
Verónica Palomera-Ávalos ◽  
Sergio López-Ruiz ◽  
Anna-Maria Canudas ◽  
Mercè Pallàs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
Target Genes ◽  
Epigenetic Inheritance ◽  
Mtor Inhibition ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Age Related ◽  
F2 Generation ◽  
Age Related Cognitive Decline

A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer’s Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.

Fischer 344 Rats Display Age-Related Memory Deficits in Trace Fear Conditioning.

2004 ◽  
Vol 118 (6) ◽  
pp. 1166-1175 ◽  
Author(s):  
Julissa S. Villarreal ◽  
James R. Dykes ◽  
Edwin J. Barea-Rodriguez
Keyword(s):  
Fear Conditioning ◽  
Memory Deficits ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Trace Fear Conditioning ◽  
Age Related ◽  
Trace Fear

Chronic antioxidant enzyme mimetic treatment differentially modulates hyperthermia-induced liver HSP70 expression with aging

2006 ◽  
Vol 100 (4) ◽  
pp. 1385-1391 ◽  
Author(s):  
Hannah J. Zhang ◽  
Susan R. Doctrow ◽  
Larry W. Oberley ◽  
Kevin C. Kregel
Keyword(s):  
Heat Stress ◽  
Recovery Period ◽  
Protein Accumulation ◽  
Mrna Levels ◽  
Hsp70 Mrna ◽  
Hsp70 Protein ◽  
Age Related ◽  
Wide Range ◽  
Old Rats ◽  
The Impact

One postulated mechanism for the reduction in stress tolerance with aging is a decline in the regulation of stress-responsive genes, such as inducible heat shock protein 72 (HSP70). Increased levels of oxidative stress are also associated with aging, but it is unclear what impact a prooxidant environment might have on HSP70 gene expression. This study utilized a superoxide dismutase/catalase mimetic (Eukarion-189) to evaluate the impact of a change in redox environment on age-related HSP70 responses to a physiologically relevant heat challenge. Results demonstrate that liver HSP70 mRNA and protein levels are reduced in old compared with young rats at selected time points over a 48-h recovery period following a heat-stress protocol. While chronic systemic administration of Eukarion-189 suppressed hyperthermia-induced liver HSP70 mRNA expression in both age groups, HSP70 protein accumulation was blunted in old rats but not in their young counterparts. These data suggest that a decline in HSP70 mRNA levels may be responsible for the reduction in HSP70 protein observed in old animals after heat stress. Furthermore, improvements in redox status were associated with reduced HSP70 mRNA levels in both young and old rats, but differential effects were manifested on protein expression, suggesting that HSP70 induction is differentially regulated with aging. These findings highlight the integrated mechanisms of stress protein regulation in eukaryotic organisms responding to environmental stress, which likely involve interactions between a wide range of cellular signals.

Sign in / Sign up

Export Citation Format

Share Document