Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism

Hopp, Sarah C.; D’Angelo, Heather; Royer, Sarah E; Kaercher, Roxanne M.; Adzovic, Linda; Wenk, Gary L.

doi:10.1016/j.neuroscience.2014.09.007

Cited by 24 publications

(20 citation statements)

References 62 publications

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“…Previous studies on the ADNI dataset have also reported significant genetic interactions for CACNA1C using Positron Emission Tomography (PET) imaging (Koran et al, 2014) and LASSO screening with candidate phenotypes (Yang et al, 2015), which all involve certain ‘ conditioning ’ for the contribution from CACNA1C to be detected. Animal AD models have confirmed several results from human studies (Hopp et al, 2014) and related pathways have been identified as a therapeutic target (Liang and Wei, 2015) for AD. Interestingly, a recent multi-site large-scale voxel level functional connectivity study, which included 939 subjects, has revealed that functional connectivity patterns in the orbitofrontal cortex region are significantly altered in depression patients (Cheng et al, 2016).…”

Section: Discussionsupporting

confidence: 52%

Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications

et al. 2017

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We propose a generalized reduced rank latent factor regression model (GRRLF) for the analysis of tensor field responses and high dimensional covariates. The model is motivated by the need from imaging-genetic studies to identify genetic variants that are associated with brain imaging phenotypes, often in the form of high dimensional tensor fields. GRRLF identifies from the structure in the data the effective dimensionality of the data, and then jointly performs dimension reduction of the covariates, dynamic identification of latent factors, and nonparametric estimation of both covariate and latent response fields. After accounting for the latent and covariate effects, GRLLF performs a nonparametric test on the remaining factor of interest. GRRLF provides a better factorization of the signals compared with common solutions, and is less susceptible to * Corresponding author at: Centre for Computational Systems Biology and School of Mathematical Sciences, Fudan University, Shanghai, PR China. jianfeng64@gmail.com (J. Feng). 1 Data used in preparation of this article were obtained from the Alzheimers Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdfThe authors report no conflict of interest. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript overfitting because it exploits the effective dimensionality. The generality and the flexibility of GRRLF also allow various statistical models to be handled in a unified framework and solutions can be efficiently computed. Within the field of neuroimaging, it improves the sensitivity for weak signals and is a promising alternative to existing approaches. The operation of the framework is demonstrated with both synthetic datasets and a real-world neuroimaging example in which the effects of a set of genes on the structure of the brain at the voxel level were measured, and the results compared favorably with those from existing approaches.

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Section: Discussionsupporting

confidence: 52%

Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications

et al. 2017

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“…In addition, increased levels of RyR1, RyR2, and RyR3 mRNA correlate negatively with the performance of aged rats in this maze (Hopp et al, 2014). Our results expand these previous findings by showing that successful performance of a different hippocampal-dependent spatial memory task promoted significant increases in the mRNA and protein levels of RyR2/RyR3 in young rat hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Aging Impairs Hippocampal- Dependent Recognition Memory and LTP and Prevents the Associated RyR Up-regulation

Arias‐Cavieres

Adasme

Sánchez

et al. 2017

Front. Aging Neurosci.

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Recognition memory comprises recollection judgment and familiarity, two different processes that engage the hippocampus and the perirhinal cortex, respectively. Previous studies have shown that aged rodents display defective recognition memory and alterations in hippocampal synaptic plasticity. We report here that young rats efficiently performed at short-term (5 min) and long-term (24 h) hippocampus-associated object-location tasks and perirhinal cortex-related novel-object recognition tasks. In contrast, aged rats successfully performed the object-location and the novel-object recognition tasks only at short-term. In addition, aged rats displayed defective long-term potentiation (LTP) and enhanced long-term depression (LTD). Successful long-term performance of object-location but not of novel-object recognition tasks increased the protein levels of ryanodine receptor types-2/3 (RyR2/RyR3) and of IP3R1 in young rat hippocampus. Likewise, sustained LTP induction (1 h) significantly increased RyR2, RyR3 and IP3R1 protein levels in hippocampal slices from young rats. In contrast, LTD induction (1 h) did not modify the levels of these three proteins. Naïve (untrained) aged rats displayed higher RyR2/RyR3 hippocampal protein levels but similar IP3R1 protein content relative to young rats; these levels did not change following exposure to either memory recognition task or after LTP or LTD induction. The perirhinal cortex from young or aged rats did not display changes in the protein contents of RyR2, RyR3, and IP3R1 after exposure at long-term (24 h) to the object-location or the novel-object recognition tasks. Naïve aged rats displayed higher RyR2 channel oxidation levels in the hippocampus compared to naïve young rats. The RyR2/RyR3 up-regulation and the increased RyR2 oxidation levels exhibited by aged rat hippocampus are likely to generate anomalous calcium signals, which may contribute to the well-known impairments in hippocampal LTP and spatial memory that take place during aging.

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“…Microglia are efficient sensors of changes in the CNS microenvironment, and their neuroprotective role has been hypothesized to be impaired during aging [ 33 ]. For instance, there is an increased expression of the interleukin (IL)-6 receptor [ 34 ], which has been associated with deficits in cognitive function, and aged animals differ from young animals in physiology, pathophysiological features, and behavioral outcome after brain injury [ 35 ]. Aged brain microglia are polarized to the M1 phenotype, with a long-lasting impairment of M2 responses after ischemic injury [ 36 , 37 ].…”

Section: Microglia In the Aged Cnsmentioning

confidence: 99%

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

Mecca

Giambanco

Donato

et al. 2018

IJMS

175

138

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Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine)-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases.

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Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism

Cited by 24 publications

References 62 publications

Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications

Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications

Aging Impairs Hippocampal- Dependent Recognition Memory and LTP and Prevents the Associated RyR Up-regulation

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

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