Dr. Benedict C. Albensi, Synaptic Plasticity and Cellular Memory Dysfunction

Dr. Benedict C. Albensi

Principal Investigator
Synaptic Plasticity and Cellular Memory Dysfunction Lab, Division of Neurodegenerative Disorders

Professor (External Adjunct)
Department of Pharmacology & Therapeutics, College of Medicine, Faculty of Health Sciences

Former Manitoba Dementia Research Chair

Former Everett Endowment Fund Chair

Research Focus

The major focus of our laboratory is to understand the biological basis of memory and to also understand what happens to memory when it is impaired. To this end, we attempt to identify molecular signalling pathways and mechanisms that could be targeted with promising therapeutics for enhancing memory and for preventing and/or reversing memory impairments, in diseases or conditions such as Alzheimer’s disease, stroke, head trauma, etc. Much of our work is centred on the signalling pathway involving the transcription factor, nuclear factor kappa B (NF-kB), which is central to not only in inflammatory processes and immune system function but also plays a central role in basic mechanisms of memory formation and recall.

Why is this work important?

It provides a valuable platform for scientists to understand how brain cells and biochemical processes change at the molecular level during the formation of normal memory
By understanding transcriptional regulation during memory encoding, we can identify a gene (or genes) that are utilized during normal memory formation
Characterizing the biological basis of normal memory will lend great insight into treating age-related central nervous system diseases and/or conditions of brain injury that contribute to memory impairment
Our research could ultimately lead to the development of new drug targets and/or new interventions to enhance normal memory and to treat memory disorders and related neurodegenerative conditions

What techniques and equipment are used in this laboratory?

Brain slice electrophysiology
Behavioral (egs., Morris water maze, Barnes maze)
Cell & molecular assays (e.g.s., Western blots, gel shifts, calcium analysis, mitochondrial function assessment, etc.)
PET/MRI scanning and cellular neuroimaging
Cell culture
Computational modelling of cellular function

For the equipment list, see https://www.sbrc.ca/dnd/dnd-research-equipment/.

About Dr. Benedict Albensi

Dr. Benedict C. Albensi, Ph.D., BCMAS, CRQM is a Professor of Pharmacology and Therapeutics at the Max Rady College of Medicine – University of Manitoba and a Principal Investigator and the Everett Endowment Fund Chair for Alzheimer’s Research at the St. Boniface Hospital Research Centre (since 2005). He is best known for his work with factors involved in ageing, cognition, and Alzheimer’s disease (AD), such as nuclear factor kappa B (NF-kB), a mediator of inflammation and a required molecule for memory. He obtained his Ph.D. in Neuroscience from the University of Utah’s Medical School in 1995. He was awarded a Postdoctoral Fellowship at Georgetown University in Washington, DC, working with Drs. Faden and Pekar, where he developed MRI methods for investigating head trauma and cognition. He then went on to work as a Postdoctoral Scholar with Dr. Mark Mattson, an internationally recognized leader in neurodegenerative research, at the Sanders-Brown Center on Aging – University of Kentucky where he was the first to show NF-kB is required for synaptic plasticity in mammals. Other appointments have included the Cleveland Clinic, NPS Pharmaceuticals, Pfizer, Case Western Reserve University. Over the last few years, his work has been largely focused on mitochondrial dysfunction in AD. Recently, the Albensi lab has shown very early deficits and sex-based differences in mitochondrial function before the appearance of plaques and tangles, the classic hallmarks of AD. He has been ranked in the top 1% worldwide by Expertscape.com for his number of publications from 2010-2020 in 7 areas including Alzheimer Disease (0.48%), neurocognitive disorders (0.76%), tauopathies (0.98%), dementia (0.85%), NF-kappa B (0.42%), memory (68%) & energy metabolism (0.68%).

For more information, please contact:

Benedict C. Albensi, Ph.D., BCMAS, CRQM
Principal Investigator
Synaptic Plasticity and Cellular Memory Dysfunction Lab, Division of Neurodegenerative Disorders

Professor
Department of Pharmacology & Therapeutics, College of Medicine, Faculty of Health Sciences, University of Manitoba

(204) 235-3941 (lab)
(204) 235-3939 (DND administrative manager)
(204) 237-4092 (fax)
balbensi@sbrc.ca

St. Boniface Hospital Albrechtsen Research Centre
351 Taché Ave.
Winnipeg, Manitoba R2H 2A6
Canada

Publications

All publications may be viewed at the following link:

https://www.ncbi.nlm.nih.gov/myncbi/benedict.albensi.1/bibliography/public/

Academic Awards

2023 Ranked #1 in Florida according to Expertscape.com for number of publications on NF-kappaB over ten years https://expertscape.com/ex/nf-kappa+b/s/fl
2022 Listed in Expertscape.com as being in the top 1% worldwide in several areas
(2012-2022) for the number of publications: Alzheimer Disease (0.30%),
neurocognitive disorders (0.43%), dementia (0.57%), NF-kappa B (0.043%),
memory (0.59%), mitochondria (0.88%), & energy metabolism (0.28%).
2020 Seminar ranked #1 out of 56 talks for number of likes at 11^th Targeting Mitochondrial Congress
2020 University of Manitoba 2019 Merit Award (research) $3,000
2020 A review of clinical treatment considerations of donepezil in severe Alzheimer’s disease, link: https://lnkd.in/evFQKqf in CNS Neuroscience & Therapeutics. Top downloaded & most read paper for 2018-2019 according to Wiley Pub.
2018 Weston Brain Institute Outstanding Achievement Award Nominee
2017 University of Manitoba Merit Award (research, service, teaching combo) $3000
Weston Brain Institute Outstanding Achievement Award 2016 Nominee
March 2013 Sanofi BioGENEius Challenge Canada Mentor Award, Wpg., MB
Sept. 2012 Richard Hoeschen Award, $1000-B.Sc.(Med) Student Supervisors, MMSF/SBGHRC, Wpg., MB
2011 to current. Everett Endowment Fund Chair
April 2007 Sanofi-Aventis Biotech Challenge Award of Appreciation, Wpg., MB
1998 U. of Kentucky Med. Ctr., Spring Neurosci. Day, 1st Prize-Best Poster (cash award)
1996 – 1997 Georgetown University Medical Center Research Fellowship
1994 William D. Carey Science Award – American Association for the Advancement of Science
1994 Medical Imaging Res. Lab Symp., Oral Finalist, Sundance, UT
1993 Graduate Research Fellowship Award, $5,000, Univ. of Utah

Active research funding

2023-2024 Restoring CAMKK2 protein levels to treat neurodegeneration in Alzheimer’s

Disease. Co-Investigator. $15,000, NSU President’s Faculty Research & Development Grant (PFRDG). #23-6470-P0001.

2023-2027 Sex-based Differences of a High Fat Diet in Alzheimer’s Disease (AD): Can Nilotinib Reverse Bioenergetic and Neuropathological Deficits? Principal Investigator (PI). NIH R16. $616,000 over 4 years. 1R16NS134540-01.

2023-2025 Effects of mild traumatic brain injury in a mouse model of cerebral amyloid angiopathy. Co-Investigator. NIH R03. $308,000 total over 2 years (ranked in top 5th percentile). 1R03AG081865-01.

2023-2028 U-RISE at Nova Southeastern University. Participant. NIH T34 U-RISE Undergraduate Research Training Initiative for Student Enhancement. $1,498,302. 1T34GM145509-01A1.

2023-2028 Perinatal nutrition strategy with omega-3 docosahexaenoic acid to protect brain in fetal alcohol spectrum disorders. Co-Applicant. $740,000 CAD total over 5 years. CIHR. Was ranked #1 out of 31 applications. #487107.

2022-2023 Repurposing cardiovascular medications for the treatment of dementia. Collaborator. $15,000, NSU President’s Faculty Research & Development Grant (PFRDG). #334867.

2019-2024 Sex-based Differences Associated with Mitochondrial Dysfunction in Alzheimer’s Disease. Canadian Inst. of Health Research (CIHR). PI. $725,985 total over 5 years (15% success rate for this grant competition; was ranked 3rd out of 6 for funded grants – 40 total grants submitted). #PJT-162144.

Past research funding

2019-2023 Effects of dietary flaxseed on memory and cognition (clinical trial in suspected Alzheimer subjects). Canadian Agricultural Partnership (CAP). PI. $430,746 total over 3 years. #1000219580.

2021-2022 Formulation and Evaluation of Rapid-Disintegrating Oral Tablets for Pediatric Preanesthesia. Principal Investigator (PI); transferred from Dr. Mastropietro. $5,000. Health Professional Division (HPD). Grant number: 334604.

2021-22 Douglas and Patricia Everett Endowment – Douglas & Patricia Everett Endowment for Alzheimer’s research (renewal). PI & Chair. Year 1, $79,875.12. Ended March 2022.

2019-2024 Canadian Dementia Strategy-Team Grant. Member. Phase II. $46 million dollars to be distributed competitively among Canadian Consortium on Neurodegeneration in Aging (CCNA) members. See announcement link: https://www.sbrc.ca/2019/06/canadian-consortium-on-neurodegeneration-in-aging-ccna-phase-2-funding-announcement-includes-mb-researchers/

2021 Contract. Research partnership with Mitrix Bio Inc. (formerly called Mitochondrial Transfusion), Pleasanton, CA, USA. PI. $38,311 CAD over 6 months.

2017-20 Douglas and Patricia Everett Endowment – Douglas & Patricia Everett Endowment for Alzheimer’s research (renewal). PI & Chair. Year 1, $64,940; Year 2, $68,282.70; Year 3, $74,074.

2015-20 Basic and Patient-Oriented Dementia Research: Linking Novel Methods for Early Stage Detection with Understanding Pathological Mechanisms in Dementia. Manitoba Dementia Research Chair Award, Research Manitoba/Alzheimer’s Society of Manitoba. PI & Chair, $500,000 total. $100,000/year over 5 years.

2014-19 Canadian Consortium on Neurodegeneration in Aging (CCNA). Team Theme 1 –Clinical Genetics and Gene Discovery. Co-applicant/Member. $6,063,172 (partial funding received for travel to meetings for trainees). Grant number: CAN 137794.

2014-19 Mitochondrial Function, Neural Plasticity, and Memory. Natural Sciences and Engineering Research Council of Canada (NSERC), Discovery Grant. PI. $130,000 total, $26,000/year over 5 years.

2017-18 St. Boniface Hospital Foundation – Donation. Brain & Nerve Disease Research. PI, $4,650.

2014-17 Douglas and Patricia Everett Endowment – Douglas & Patricia Everett Endowment for Alzheimer’s research. PI & Chair. Year 1, $42,697; Year 2, $54,320. Year 3, $60,974.
2015-16 High Resolution Magnetic Resonance Microscopy Centre. Strategic Investment in Research and Innovation (SIRI) Grant. Research Manitoba. Collaborator (Dr. Melanie Martin, PI). $212,165 total. Year 1, $187,165; Year 2, $25,000.

2014-15 St. Boniface Hospital Foundation – Donation. Alzheimer’s research. PI, $4,650.

2014-15 Edward Family Endowment. Donation. Alzheimer’s research. PI, $100,000 total.

2011-14 Douglas and Patricia Everett Endowment. Donation. Alzheimer’s research. PI & Chair. Year 1, $40,559; Year 2, $24,466; Year 3, $35,663.

2012 Novel Technology for Early Diagnosis of Alzheimer Disease using Virtual Reality Psychophysical Experiments. Collaborative Health Research Projects (CHRP) sponsored by NSERC/CIHR, Industrial Technology Ctr. Co-PI, $50,000.

2009-14 The Role of p50 NF-kB and Egr-2 in Long Term Potentiation and Memory. Natural Sciences and Engineering Research Council of Canada (NSERC), Discovery Grant. PI. $125,000 total, $25,000/year over 5 years.

2008-13 Regulation of Brain Adenosine Levels by Ecto-enzymes and Membrane Transporters. CIHR, Operating Grant. Co-PI, $599,205 total, ~$119,841/year over 5 years.

2010-12 Stroke Injury in Genetic Mouse Models. Heart and Stroke Foundation of Canada (HSFC), Renewal, Co-PI, $100,000 total, $50,000/year over 2 years.

2008-10 Hippocampal Gene Expression Profiling and the Possible Involvement of Homer1 in Alzheimer’s Disease. Alzheimer’s Society of Canada. Principal Applicant, $130,000 total, $65,000/year over 2 years.

2009-10 Memory-Associated Gene-Expression Profiling During Aging. University of Manitoba’s Centre on Aging, Operating Grant, PI, $10,000 total over 1 year.

2009 CFI-Partnering Grant. St Boniface Hospital and Research Foundation, Open Grants Competition, PI, $6,500 total over one year.

2008-10 Stroke Injury in Genetic Mouse Models. Heart and Stroke Foundation of Canada (HSFC), Co-PI, $90,000 total, $45,000/year over 2 years.

2005-10 Multidisciplinary 2-Photon Imaging of Calcium and Mitochondrial Dysregulation in Intact Tissues. Canada Foundation for Innovation (CFI) – Equipment Grant, Co-PI, $1,004,835 total over 5 years.

2007-09 Regulation of Adenosine Levels. CIHR, Operating Grant (funded by RPP – MHRC). Co-Applicant, $182,184 total, $91,092/year.

2006-09 The Role of sAPP and NF-kB in Alzheimer’s Disease, Scottish Rite Charitable Foundation of Canada, PI, $105,000 total, $35,000/year over 3 years.

2006-09 Roles for PS1 Mutations, Calcium Overload, and NF-kB Activation in Synaptic and Cognitive Dysfunction, MHRC, Establishment grant. PI, $100,000 total, ~$33,333/year over 3 years.

2007-08 Regulation of GABAergic Interneuron Migration and Differentiation in the Vertebrate Forebrain by DLX Transcription Factors. Manitoba Inst. of Child Health (MICH), Operating Grant. Co-Applicant, $45,000 total, $22,500/year over 2 years.

2006-08 Roles of PS1 Mutations and NF-kB in Synaptic Plasticity and Alzheimer’s Disease, Manitoba Health Research Council (MHRC), Operating grant. PI, $100,000 total, $50,000/year over 2 years.

2007 Programmable Stimulus Generator and Multielectrode Array to Investigate New Electrical Stimulation Protocols for Relief from Seizure-Like Activity, Natural Sciences & Research Council of Canada (NSERC), Research Tools & Instruments Grant. Co-Applicant, $79,835 total over one year.

2007 Diffusion-Weighted Imaging for Identifying Markers Associated with Brain Injury Leading to Alzheimer’s Disease. Manitoba Medical Service Foundation (MMSF), PI., $35,000 total 1 year.

2006-07 Multidisciplinary 2-Photon Imaging of Calcium and Mitochondrial Dysregulation in Intact Tissues. Canada Foundation for Innovation (CFI) – Infrastructure Support, Co-PI, $119,000 total over 2 years.

2006-07 Novel Electrical Stimulation Protocols for Relief From Epileptic Seizure-Like Activity, Dr. Paul H.T. Thorlakson Foundation Fund, Co-PI, $29,500 total over 2 years.

2005 Start-Up Operating Funds. St. Boniface General Hospital Research Foundation and University of Manitoba (VP Research office; Dean of Medicine office; Dept. of Pharmacology & Therapeutics), PI, Staff Budgets for 3 yrs: $50,000/yr, (St. Boniface). Supplies/equipment: $150,000 (Univ. Manitoba and St. Boniface); Total $300,000.

2002 A Model of the Human Blood Brain Barrier Using Human Endothelial and Glial Cells. Berkeley Citizens Commission/Bayer Pharmaceutical Division, PI, $25,000 USD total.

1997-98 MRI of Brain Injury in TNF Double Knock-Out Mice. Univ. of Kentucky, MRI Center Pilot Project Grant Award (during postdoc. appointment), PI, $1,125 USD total.

1996-97 Postdoctoral Fellowship, Georgetown Institute for Cognitive and Computational Sciences and Department of Neurology, Georgetown University Medical Center, Advisor: James Pekar, Ph.D., Washington, DC. $32,000/year.

1993-94 MRI of Hypoxic-Ischemic Injury in Neonatal Mice. Univ. of Utah Graduate Research Fellowship Grant (during PhD studies), PI, $5,000 USD total.

Dr. Wanda Snow

Dr. Wanda Snow Several transcription factors, key regulators of gene expression, have been implicated in Alzheimer’s disease. The transcription factor nuclear factor kappa B (NF-κB) is best known for its role in inflammation, but more recent studies implicate this factor in synaptic plasticity, learning, and memory. In Alzheimer’s disease, characterized by severe memory deficits, levels of this important gene regulator are altered. Creatine, an endogenous amino acid that regulates cellular energy, has been shown to activate NF-κB in neurons. Supplementation with creatine has been shown to enhance brain function and memory in healthy individuals and has been studied in clinical trials of neurodegenerative diseases, such as Parkinson’s disease. It has not, however, been investigated as a potential therapy for Alzheimer’s disease. As a postdoctoral fellow in Dr. Albensi’s lab, I am currently carrying out several projects looking at the effects of creatine, including its effects on energy and transcriptional regulation in isolated neurons and its effects on memory and brain bioenergetics in healthy mice and in a mouse model of Alzheimer’s disease in the hopes of understanding if NF-κB signaling mediates the neurobeneficial effects of creatine. In addition, I am investigating plasticity-induced expression of the transcription factor early growth response-2 , also implicated in memory and a gene target of NF-κB, in the normal and AD-like mouse hippocampus using long-term potentiation. These studies are aimed at determining which transcriptional networks are affected in Alzheimer’s disease in efforts to uncover how memory becomes compromised in the disease and how best to treat or prevent memory impairments. This work was generously supported by a postdoctoral fellowship from Research Manitoba.

Dr. Jelena Djordjevic

Dr. Jelena Dordevic Alzheimer’s disease (AD) is a late-onset, progressive, neurodegenerative disorder, characterized by cognitive and memory decline, speech loss and personality changes, affecting almost 1 million elderly in Canada alone. Besides plaques and tangles, a cascade of other pathological events ranging from synaptic dysfunction, oxidative stress, mitochondrial dysfunction, and neuroinflammation, are routinely detected in patients. Some scientists suspect that brain metabolism and mitochondrial function become altered early in AD, and these alterations, which include deficits in ATP generation, may be gender dependent. The focus of my research is centered on the mitochondrial bioenergetics in animal models engineered to mimic the brain pathology seen in Alzheimer’s disease (3xTg and CRND8 mice), since mitochondria play active roles in synaptogenesis and morphological and functional responses to synaptic activity. The goal is to characterize the mitochondrial impairments at different points in disease progression, to address sex differences in mitochondrial dysfunction in AD, and to establish the connection with inflammatory signaling, which is known to affect brain energy metabolism. This work was generously supported by a postdoctoral fellowship from Research Manitoba.

Dr. Aida Adlimoghaddam

Dr. Aida Adlimoghaddam Currently, as a postdoctoral fellow, I am working on two main projects:

First project: How memory is impaired by Alzheimer’s disease (AD; most common form of dementia) and vascular dementia (VD; second most common form of dementia). To discriminate these different type of dementia, I am using both in vitro and in vivo mouse models of AD and VD in conjunction with pathological/inflammatory markers, cell and molecular techniques, electrophysiological methods, and neuroimaging.

Second project: The characterization of an altered ammonia transport system that contributes to AD. My focus is to investigate the effects of ammonia exposure on the brain nitrogen transport system and brain mitochondrial function using an in vitro mouse model of AD. I am a recipient of a Research Manitoba Fellowship to investigate the second project.

My long-term goal for both projects is to develop new treatments for improving memory as a result of the mentioned diseases/conditions.