A5010835197- Neuroscience and Neuropharmacology Research
- Electroconvulsive Therapy Studies
- Neurological and metabolic disorders
- Treatment of Major Depression
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Alzheimer's disease research and treatments
- Alcoholism and Thiamine Deficiency
- Pharmacological Receptor Mechanisms and Effects
- Epilepsy research and treatment
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Attention Deficit Hyperactivity Disorder
- Schizophrenia research and treatment
- Diet and metabolism studies
- Tryptophan and brain disorders
- Alcohol Consumption and Health Effects
- Cancer Treatment and Pharmacology
- Cannabis and Cannabinoid Research
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Drug-Induced Ocular Toxicity
- Child and Adolescent Psychosocial and Emotional Development
- Poisoning and overdose treatments
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
University of Saskatchewan
2015-2024
University of Washington
2017
Columbia University
2017
Massachusetts General Hospital
2017
Harvard University
2017
Dalhousie University
2017
Biotechnology Research Institute
2003
National Academies of Sciences, Engineering, and Medicine
2000
Hôpital Saint-Luc
1993-1998
Université de Montréal
1993-1997
Abstract Neuroanatomical studies suggest that neuronal atrophy and destruction occur over the course of many years in neurodegenerative conditions such as schizophrenia Alzheimer's disease. In schizophrenia, early intervention with atypical neuroleptics olanzapine has been shown to prevent development some more serious debilitating symptoms patients. The mechanisms whereby slows or prevents symptom progression remain unclear. A previous study found increased mRNA for copper/zinc isoform...
The lacunar-canalicular network (LCN) of bone contains osteocytes and their dendritic extensions, which allow for intercellular communication, are believed to serve as the mechanosensors that coordinate processes modeling remodeling. Imbalances in remodeling, example, linked disease, including fragility associated with aging. We have reported there is a reduction scale one component LCN, osteocyte lacunar volume, across human lifespan females. In present study, we explore hypothesis...
The pool of β-Amyloid (Aβ) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity roles for Aβ peptides. We examined how naturally occurring variant, e.g. Aβ(1-38), interacts with the AD-related Aβ(1-42), predominant physiological Aβ(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, surface plasmon resonance reveal that Aβ(1-38) differently Aβ(1-40) Aβ(1-42) and, general, interferes...
Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present preliminary data seven participants from in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study an open-label, prospective, dose-escalation trial. Participants received escalating doses a Cannabis Herbal Extract (CHE) preparation 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored daily logs,...
SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation several cell signaling pathways, specificity which dictated by intrinsic affinity SH2 domains for flanking sequences phosphotyrosine residues. By using a modified yeast two-hybrid system and SHP-1 as bait, we have cloned human cDNA, PILRα, encoding 303-amino acid immunoglobulin-like transmembrane receptor bearing two cytoplasmic tyrosines positioned within an immunoreceptor tyrosine-based inhibitory...
Hyperhomocysteinemia is associated with an increased risk of Alzheimer's disease (AD). Our previous work has demonstrated that combined folate and vitamin B12 (vit-B12) supplementation prevents tau hyperphosphorylation memory deficits induced by
Monoamine oxidase-A (MAO-A) and MAO-B have both been implicated in the pathology of Alzheimer disease (AD). We examined 60 autopsied control AD donor brain samples to determine how well MAO function aligned with two major risk factors for AD, namely sex APOE epsilon4 status. MAO-A activity was increased cortical, but not hippocampal, samples. In contrast, regions (with a strong input from female donors) whether sample means were compared based on: (a) diagnosis alone; (b) diagnosis-by-APOE...
Abstract: Altered biogenic amine metabolism and function are believed to underlie certain of the neuropsychiatric symptoms, e.g., depression, mania, anxiety, encountered in clinical hepatic encephalopathy (HE). We therefore investigated activity degradative enzyme monoamine oxidase (MAO) its binding parameters using [ 3 H]Ro 41‐1049 (defining MAO‐A) 19‐6327 (Lazabemide; defining MAO‐B) autopsied brain tissue from male cirrhotic patients with HE. The MAO‐B HE patient were not significantly...
We have demonstrated recently that atypical antipsychotics possess neuroprotective actions in H2O2-mediated and serum-withdrawal models of cell death. In the present study, we compared ability typical to protect against an insult mediated by Abeta(25-35), apoptogenic fragment Alzheimer's disease-related beta-amyloid (Abeta) peptide. Treatment PC12 cultures with Abeta(25-35) did not significantly alter total cellular expression levels Bax, a proapoptotic Bcl-2 family member, or Bcl-XL,...
Methylglyoxal (MG), a reactive dicar-bonyl molecule, can modify protein to form advanced glycation endproducts. Increased MG level has been implicated in proliferative vascular diseases, but the underlying mechanisms are not clear yet. The serine/ threonine kinase, Akt, regulates multiple signaling pathways that control cell proliferation. Using mass spectrometric analysis, we have detected modification of Akt1 by at Cys77. This structural increased phosphorylation Ser473 and Thr308....
Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, do not overexpress the HER2 receptor represent most aggressive subtype, which is characterised by resistance to therapy in frequently relapsing a high rate patient mortality. This likely due slowly proliferating tumour-initiating cells (TICs), understanding molecular mechanisms control TICs behaviour crucial for development effective therapeutic approaches. Here, we present our novel...
Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality life children affected by epileptic encephalopathies. With limited access CBD, Cannabis extracts oil are becoming increasingly available. Physicians show reluctance recommend given lack high safety data especially regarding potential for harm caused other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims study presented this...
The APOE ε4 allele was originally reported to contribute risk of Alzheimer's disease (AD) in women, yet male and female AD patient-derived data are routinely pooled. Histopathological hallmarks include neurofibrillary tangles centered on hyperphosphorylated Tau plaques composed the β-amyloid (Aβ) peptide that is derived by sequential secretase-mediated cleavage Amyloid Protein Precursor (APP). We chose examine profiles Aβ(1-40), Aβ(1-42), N-truncated (i.e., p3-related) fragments...
// Chelsea E. Cunningham 1, * , Shuangshuang Li Frederick S. Vizeacoumar Kalpana Kalyanasundaram Bhanumathy 1 Joo Sang Lee 2 Sreejit Parameswaran Levi Furber Omar Abuhussein 3 James M. Paul Megan McDonald Shaina D. Templeton Hersh Shukla Amr El Zawily Boyd Nezeka Alli Darrell Mousseau 4 Ron Geyer Keith Bonham 5 Deborah H. Anderson Jiong Yan Li-Yuan Yu-Lee 6 Beth A. Weaver 7 Maruti Uppalapati Eytan Ruppin Anna Sablina 8 Andrew Freywald Franco J. 3, Department of Pathology, Cancer Cluster,...
Human brain organoids are emerging as translationally relevant models for the study of human health and disease. However, it remains to be shown whether human-specific protein processing is conserved in organoids. Herein, we demonstrate that cell fate composition unguided dictated by culture conditions during embryoid body formation, at this stage can optimized result presence glia-associated proteins neural network activity early three-months vitro. Under these conditions, generated from...
Abstract The p38 mitogen‐activated protein kinase (MAPK) cascade as well the enzyme monoamine oxidase‐A (MAO‐A) have both been associated with oxidative stress. We observed that specific inhibition of p38(MAPK) [using either a chemical inhibitor or dominant‐negative clone] selectively induces MAO‐A activity and MAO‐A‐sensitive toxicity in several neuronal cell lines, including primary cortical neurons. Over‐expression constitutively active results phosphorylation activity. MAO‐A(Ser209Glu)...