scholarly journals Cerebrovascular response to exercise interacts with individual genotype and amyloid-beta deposition to influence response inhibition with aging

2021 ◽  
Author(s):  
Jacqueline Palmer ◽  
Carolyn S Kaufman ◽  
Eric D. Vidoni ◽  
Robyn A. Honea ◽  
Jeffrey M. Burns ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Response Inhibition ◽  
Executive Dysfunction ◽  
Moderate Intensity ◽  
Carrier Status ◽  
Brain Pathology ◽  
Individual Genotype ◽  
Cerebrovascular Function ◽  
Structural Brain

The etiology of cognitive dysfunction associated with Alzheimer's disease (AD) and dementia is multifactorial. Yet, mechanistic interactions among key neurobiological factors linked to AD pathology are unclear. This study tested the effect of interactions between cerebrovascular function, individual genotype, and structural brain pathology on response inhibition performance, an early and sensitive indicator of cognitive executive dysfunction with aging. We quantified cerebrovascular response (CVR) to moderate-intensity aerobic exercise using transcranial doppler ultrasound and global amyloid-beta (Aβ) deposition using positron emission tomography in a group of cognitively normal older adults genotyped as APOE4 carriers and noncarriers. We quantified response inhibition during a cognitive Stroop test. Individuals with blunted CVR possessed greater Aβ deposition. There was CVR-by-carrier status-by-Aβ interaction on response inhibition. Blunted CVR was associated with impaired response inhibition specifically in carriers. Despite having greater Aβ deposition, carriers with higher CVR demonstrated better response inhibition. Cerebrovascular interactions with individual genotype and structural brain pathology may provide a physiologically-informed target for precision-medicine approaches for early treatment and prevention of cognitive dysfunction with aging.

scholarly journals Remodeling Alzheimer-amyloidosis models by seeding

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brittany S. Ulm ◽  
David R. Borchelt ◽  
Brenda D. Moore
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Time Interval ◽  
Murine Models ◽  
Brain Pathology ◽  
Amyloid Deposits ◽  
Transgenic Murine Models ◽  
Mutant Genes

AbstractAlzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.

scholarly journals Inhibition of PDE4 by Roflumilast ameliorates sleep deprivation-induced cognitive dysfunction in C57BL/6J mice

2021 ◽  
Author(s):  
Abid Bhat ◽  
Muhammed Bishir ◽  
SR. Pandi-Perumal ◽  
Sulie Chang ◽  
Saravana Babu Chidambaram
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Recognition Task ◽  
Synaptic Proteins ◽  
Pde4 Inhibitor ◽  
Long Term Memory ◽  
Synapsin I ◽  
Memory Assessment ◽  
Novel Object Recognition Task

Sleep deprivation interferes with long-term memory and cognitive functions by over-activation of phosphodiesterase (PDE) enzymes. PDE4 is a non-redundant regulator of the cyclic nucleotides (cAMP), is densely expressed in the hippocampus, and is involved in learning and memory processes. In the present study, we investigated the effects of Roflumilast (ROF), a PDE4 inhibitor, on sleep deprivation induced cognitive dysfunction in a mouse model. Memory assessment was performed using a novel object recognition task and the cAMP level was estimated by ELISA. The alterations in the expressions of PDE4B, amyloid beta, CREB, BDNF, and synaptic proteins (Synapsin I, SAP 97, PSD 95) were assessed to gain insights on the possible mechanisms of action of ROF using the western blot technique. Results show that ROF reverse SD induced cognitive decline in mice. ROF down-regulated PDE4B and amyloid beta expressions. Additionally, ROF improved cAMP levels and the expressions of synapsin I, SAP 97, and PSD 95 in the hippocampal region of SD mice. Taken together, these results suggest that ROF can suppress the deleterious effects of SD-induced cognitive dysfunction via PDE4-mediated cAMP/CREB/BDNF cascade.

scholarly journals Oral Administration of Alpha Linoleic Acid Rescues Aβ-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 667 ◽  
Author(s):  
Waqar Ali ◽  
Muhammad Ikram ◽  
Hyun Young Park ◽  
Min Gi Jo ◽  
Rahat Ullah ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Apoptotic Cell ◽  
Cell Loss ◽  
Treated Mouse ◽  
Omega 3 ◽  
Memory Dysfunction ◽  
Apoptotic Markers ◽  
Elevated Expression

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aβ1–42 (Aβ1–42, 5 μL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aβ1–42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aβ1–42-injected mice to a greater extent than the Aβ1–42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aβ1–42 infused mouse brains; interestingly, these markers were significantly reduced in the Aβ + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aβ1–42-treated mouse brains, whereas these markers were markedly reduced in the Aβ + ALA-cotreated group. Moreover, Aβ1–42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aβ1–42) in the mouse brains, whereas these proteins were markedly reduced in the Aβ + ALA-cotreated group. We also checked the effects of ALA against Aβ-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aβ-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aβ + ALA-cotreated mouse brains.

scholarly journals Aromatherapy improves cognitive dysfunction in senescence-accelerated mouse prone 8 by reducing the level of amyloid beta and tau phosphorylation

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240378
Author(s):  
Michiaki Okuda ◽  
Yuki Fujita ◽  
Yuki Takada-Takatori ◽  
Hachiro Sugimoto ◽  
Katsuya Urakami
Keyword(s):  
Cognitive Dysfunction ◽  
Amyloid Beta ◽  
Tau Phosphorylation ◽  
Senescence Accelerated Mouse

scholarly journals Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise

2017 ◽  
Vol 122 (5) ◽  
pp. 1125-1133 ◽  
Author(s):  
Sandra A. Billinger ◽  
Jesse C. Craig ◽  
Sarah J. Kwapiszeski ◽  
Jason-Flor V. Sisante ◽  
Eric D. Vidoni ◽  
...  
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Dynamic Response ◽  
Moderate Intensity ◽  
Artery Blood Flow ◽  
Moderate Intensity Exercise ◽  
Cerebrovascular Function ◽  
Exercise Response ◽  
Response Profile ◽  
Health And Disease

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease. NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.

Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice

2009 ◽  
Vol 35 (3) ◽  
pp. 406-414 ◽  
Author(s):  
Xin-Kang Tong ◽  
Nektaria Nicolakakis ◽  
Priscilla Fernandes ◽  
Brice Ongali ◽  
Jonathan Brouillette ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyloid Beta ◽  
Cerebrovascular Function ◽  
And Oxidative Stress

scholarly journals Change in diagnostic confidence brought about by using in utero MRI for fetal structural brain pathology: analysis of the MERIDIAN cohort

2017 ◽  
Vol 72 (6) ◽  
pp. 451-457 ◽  
Author(s):  
P.D. Griffiths ◽  
M. Bradburn ◽  
M.J. Campbell ◽  
D.J.A. Connolly ◽  
C.L. Cooper ◽  
...  
Keyword(s):  
In Utero ◽  
Brain Pathology ◽  
Diagnostic Confidence ◽  
Structural Brain
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