Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neuroscience Institute
Total Results:
13358
SLEEP SPINDLE COUNT IN SUBSYNDROMAL DEPRESSED VS NORMAL ELDERLY: A PROTECTIVE EFFECT OF SLEEP SPINDLES? [Meeting Abstract]
ISI:000431183401175
ISSN: 1550-9109
CID: 3114152
American journal of respiratory & critical care medicine. 2018:197(7):933-943.DOI: 10.1164/rccm.201704-0704OC
Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study
RATIONALE: Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVE: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS: Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 to 90, were non-depressed and had a consensus clinical diagnosis of cognitively normal. CSF Amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B Positron Emission Tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS: We found that severity of OSA indices (lnAHIall [F1,88=4.26, p<.05] and lnAHI4% [F1,87=4.36, p<.05]) were associated with annual rate of change of CSF Abeta42 using linear regression after adjusting for age, sex, BMI and ApoE4 status. LnAHIall and lnAHI4 were not associated with increases in ADPiB-mask most likely due to the small sample size although there was a trend for lnAHIall (F1,28=2.96, p=.09 and F1,28=2.32, n.s. respectively). CONCLUSION: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2 year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.
PMCID:6020410
PMID: 29125327
ISSN: 1535-4970
CID: 2772892
Real-time particle filtering and smoothing algorithms for detecting abrupt changes in neural ensemble spike activity
Sequential change-point detection from time series data is a common problem in many neuroscience applications, such as seizure detection, anomaly detection, and pain detection. In our previous work (Chen et al., 2017, J. Neural Eng.), we have developed a latent state space model, known as Poisson linear dynamical system (PLDS), for detecting abrupt changes in neuronal ensemble spike activity. In online brain-machine interface (BMI) applications, a recursive filtering algorithm is used to track the changes in the latent variable. However, previous methods have restricted to Gaussian dynamical noise and have used Gaussian approximation for the Poisson likelihood. To improve the detection speed, we introduce non-Gaussian dynamical noise for modeling a stochastic jump process in the latent state space. To efficiently estimate the state posterior that accommodates non-Gaussian noise and non-Gaussian likelihood, we propose particle filtering and smoothing algorithms for the change-point detection problem. To speed up the computation, we implement the proposed particle filtering algorithms using advanced GPU (graphic processing unit) computing technology. We validate our algorithms using both computer simulations and experimental data for acute pain detection. Finally, we discuss several important practical issues in the context of real-time closed-loop BMI applications.
PMCID:5966736
PMID: 29357468
ISSN: 1522-1598
CID: 2929372
Utilization of Immunotherapy in Head and Neck Cancers Pre-Food and Drug Administration Approval of Immune Checkpoint Inhibitors [Meeting Abstract]
ISI:000428145600179
ISSN: 0360-3016
CID: 3035562
18F-florbetapir Positron Emission Tomography-determined Cerebral beta-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery
BACKGROUND:Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS:Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS:The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS:In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.
PMCID:5849499
PMID: 29389750
ISSN: 1528-1175
CID: 2994312
CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation (MCS)
Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer's disease (AD), there is a lack of systematic assessments of gene expression and encoded proteins within individual vulnerable cell populations, precluding translational investigations at the molecular and cellular level. Further, no effective treatment exists to combat intellectual disability and basal forebrain cholinergic neurodegeneration seen in DS. To further our understanding of gene expression changes before and following cholinergic degeneration in a well-established mouse model of DS/AD, the Ts65Dn mouse, we assessed RNA expression levels from CA1 pyramidal neurons at two adult ages (∼6 months of age and ∼11 months of age) in both Ts65Dn and their normal disomic (2N) littermates. We further examined a viable therapeutic, maternal choline supplementation (MCS), which has been previously shown to lessen dysfunction in spatial cognition and attention, and have protective effects on the survival of basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model. Results indicate that MCS normalized expression of several genes in key gene ontology categories, including synaptic plasticity, calcium signaling, and AD-associated neurodegeneration related to amyloid-beta peptide (Aβ) clearance. Specifically, normalized expression levels were found for endothelin converting enzyme-2 (Ece2), insulin degrading enzyme (Ide), Dyrk1a, and calcium/calmodulin-dependent protein kinase II (Camk2a), among other relevant genes. Single population expression profiling of vulnerable CA1 pyramidal neurons indicates that MCS is a viable therapeutic for long-term reprogramming of key transcripts involved in neuronal signaling that are dysregulated in the trisomic mouse brain which have translational potential for DS and AD.
PMCID:5874173
PMID: 29394516
ISSN: 1098-1063
CID: 2933942
Advanced DWI Methods for the Assessment of Ischemic Stroke [Comment]
OBJECTIVE:This commentary discusses recent preclinical research on the potential feasibility and benefits of applying advanced DWI methods for the assessment of acute stroke. CONCLUSION:A DWI parameter known as kurtosis shows promise in helping to identify tissue that is likely salvageable at reperfusion.
PMID: 29446676
ISSN: 1546-3141
CID: 4452232
Phase-controlled, speckle-free holographic projection with applications in precision optogenetics
Holographic speckle is a major impediment to computer-generated holographic (CGH) projections in applications ranging from display, optical tweezers, and machining to optogenetic neural control. We present an iterative phase retrieval algorithm that allows the projection of amplitude-controlled speckle-free one-dimensional patterns with a high degree of pattern uniformity. The algorithm, termed the weighted Gerchberg-Saxton with phase-control (GSW-PC), is shown to have the ability to simultaneously control both the phase and amplitude of projected patterns with high diffraction efficiencies. Furthermore, we show that the framework can address the challenge of projecting volumetric phase and amplitude-controlled patterns, by incorporating GSW-PC with the angular spectrum method. The algorithms' performance is numerically and experimentally tested, and further compared with conventional and modern CGH techniques.
PMCID:5852266
PMID: 29564366
ISSN: 2329-423x
CID: 3000982
Small molecule antagonists of RAGE-DIAPH1: Novel therapeutic opportunities in metabolic and chronic disease [Meeting Abstract]
Our previous work has shown that the cytoplasmic tail (ct) of RAGE is essential for RAGE ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE signaling requires interaction of ctRAGE with the intracellular effector, mammalian diaphanous 1, or DIAPH1. Given the complex, multi-ligand nature of ligands binding to the extracellular domains of RAGE, we sought to discover small molecule inhibitors of the interaction of ctRAGE with DIAPH1. Prompted by our identification of 13 small molecules that block the interaction of ctRAGE-DIAPH1, we pursued structure-activity relationship experiments to identify analogues potentially able to delay or prevent the progression of RAGE-related chronic diseases, such as diabetes. In vitro binding studies Native tryptophan fluorescence experiments were conducted using 1mM of compound dissolved in phosphate buffer and DMSO. 10 nM ctRAGE solution was titrated from 0.1 nM-100 muM and the dissociation constants, Kd, were estimated from the changes in peak fluorescence intensities as a function of the free compound concentration. NMR experiments were performed operating at 1H frequencies of 500 MHz and 700 MHz. NMR samples contained 50 muM of [U-15N] ctRAGE and 10 muM of the compound. All spectra were collected at 298K, which yielded high quality NMR spectra of [U-15N] RAGE tail. Compound binding to ctRAGE was identified as at least a 0.01 ppm change in the ctRAGE chemical shift. Small molecule leads were identified and referred to as NYU 1-5 (Table 1). Ex vivo biological activity assays Inhibition of smooth muscle cell (SMC) migration induced by RAGE ligands after incubation with indicated NYU compounds. SMCs were grown to confluence and starved overnight. The next morning, the medium was removed, compounds were added and the monolayer was wounded using a p200 pipette tip and allowed to incubate for 1.5h. Following incubation, compounds were removed and fresh medium containing the RAGE ligand, CML-AGE (10 mug/ml) was added for 4h. Images were taken, measured and an area ingrowth of effective migrating cells was calculated (Table 1). In vivo studies (A) Delayed type hypersensitivity. Female CF-1 mice were sensitized over the left inguinal lymph node with a methylated bovine serum albumin emulsion. On day 19 and 20 after sensitization, mice received, by oral gavage, the test compounds (5 mg/kg/bw) or vehicle twice daily. Post-final compound injection, mBSA was injected into the left hind paw. Inflammation was assessed using a semiquantitative scoring system (Figure 1). (B) Myocardial infarction in diabetic mice. Male C57BL/6 mice were rendered diabetic with STZ and were diabetic for 2 months. Mice were subjected to left anterior descending coronary artery occlusion followed by reperfusion (LAD/reperfusion). After 48h, the hearts were excised. TTC and Evan's blue staining was used to measure infarct area. Mice received a total of 7 doses of either VEHICLE or an NYU compound (Figure 2). In summary, refined compounds that inhibit the interaction of ctRAGE with DIAPH1, which exhibit in vitro and in vivo inhibition of RAGE-dependent molecular processes, present attractive scaffolds for the development of therapeutics against RAGE-mediated diseases, such as those linked to diabetic complications and chronic inflammation. We conclude that these identified compounds hold significant potential as druggable scaffolds for further development and testing for the treatment of RAGE-related disorders
EMBASE:622545638
ISSN: 1530-6860
CID: 3160432
Future prospects and challenges for Alzheimer's disease drug development in the era of the NIA-AA Research Framework [Editorial]
PMID: 29653605
ISSN: 1552-5279
CID: 3058942
