Research team
Expertise
My academic training have provided me with an extensive background in multiple biomedical disciplines including, molecular biology, biochemistry, anatomy, physiology, (histo)pathology, genetics and in particular, neuroscience and neuroimaging. I joined the Bio-Imaging lab during as a master student, during which I conducted research with Prof. Dr. Georgios A. Keliris and Dr. Lore Peeters. We investigated the effects of chemogenetic activation of basal forebrain cholinergic neurons on whole-brain functional connectivity, which resulted in my first publication as a first author in iScience. This was my first experience with preclinical magnetic resonance imaging (MRI) and manipulation of neural circuits (DREADDs) aimed at understanding the brain. I continued as a PhD student at the Bio-Imaging lab under the supervision of Prof Keliris and Prof. Dr. Marleen Verhoye. My research focused on alterations in whole brain connectivity patterns, sleep behavior and hippocampal activity during presymptomatic stages of Alzheimer’s Disease (AD). I used a multimodal approach, combining resting state functional MRI (rsfMRI), hippocampal local field potentials, biochemical analyses, and histological analyses in order to detect alterations in synaptic function and network activity during early stages of AD. Moreover, I tried to identify early disease mechanisms contributing to the early alterations in network activity. To do so, I have, together with my supervisors, implemented dynamic analyses methods for rsfMRI data and hippocampal electrophysiology in freely behaving rats in the lab. These challenging projects thought me valuable research skills including stereotactic surgery, MRI acquisition and analysis, electrophysiology acquisition, analysis is of local field potentials, Matlab coding and statistics. Moreover, my research resulted in several first author publications in journals such as Alzheimer’s Disease and Therapy, iScience and Frontiers in Aging Neuroscience. I also contributed to the standardization of preclinical rsfMRI where we developed a standard rat protocol. This resulted in a co-authorship on a Nature Neuroscience paper. I have presented my research results during numerous international conferences including European molecular imaging meeting, Society for Neuroscience and Alzheimer’s Disease and Parkinson’s disease conference. I received several presentation and poster awards for my scientific contributions. For my postdoctoral research career, I will continue to unravel mechanisms underlying the previously observed synaptic dysfunction during preclinical stages of AD.
From Neuronal Firing to Fluid Flow: Dissecting the Role of Noradrenergic Neurons in Glymphatic Dysfunction in Alzheimer's Disease
Abstract
Alzheimer's disease (AD) is the leading cause of dementia worldwide, yet effective disease-modifying therapies remain elusive. While amyloid-β (Aβ) and tau aggregation have long been considered central to AD pathology, emerging evidence indicates that disturbances in brain homeostasis and waste clearance may play a crucial, early role in disease initiation and progression. The glymphatic system facilitates cerebrospinal fluid transport through the brain, enabling the clearance of metabolic waste products including Aβ and tau. Its function is highly state-dependent, with clearance markedly enhanced during sleep. Fluctuations in norepinephrine (NE) levels during non-rapid eye movement (NREM) sleep have been shown to promote glymphatic flow. The Locus Coeruleus (LC), the brain's primary source of NE, regulates arousal and sleep–wake states and is one of the first regions to exhibit tau pathology in AD. Recent studies using the TgF344-AD rat model have shown that early hyperphosphorylated tau accumulation in the LC induces neuronal hyperactivity, specifically increasing phasic firing of LC-NE neurons. This phasic LC activity is known to be important in the transition from NREM to REM sleep. Moreover, this hyperactivity during REM sleep could be detrimental, as LC activity should be completely diminished during REM sleep. In my own research, I've observed aberrant brain activity and alterations in sleep micro- and macroarchitecture, mainly during REM sleep, in the same rat model at the same ages, supporting the hypothesis that increased LC activity could be a strong contributor to altered sleep patterns in AD. As the phasic LC activity during NREM sleep is the most important driver of the NE fluctuations which promote glymphatic clearance, I hypothesize that the hyperactivity observed in TgF344-AD rats, could also have a negative impact on the glymphatic clearance. This project aims to (1) determine how LC hyperactivity influences glymphatic transport, and (2) assess whether chemogenetic inhibition of LC neurons can restore normal clearance function. To address these objectives, I will use chemogenetic tools to selectively inhibit LC neurons in TgF344-AD rats and evaluate glymphatic flow through fluorescent tracer infusion into the cisterna magna. By integrating cell-type specific neuromodulation of LC-NE neurons with quantitative analysis of glymphatic transport, this study will reveal how early LC dysfunction affects brain clearance mechanisms. Uncovering this relationship may identify LC activity and glymphatic efficiency as modifiable early contributors to AD progression and inform new therapeutic strategies aimed at restoring sleep-dependent brain homeostasis.Researcher(s)
- Promoter: van den Berg Monica
Research team(s)
Project type(s)
- Research Project
Elucidating the role of Locus Coeruleus hyperactivity on sleep micro- and macroarchitecture in early AD.
Abstract
Sleep serves essential functions for brain health. In Alzheimer's Disease (AD), changes in sleep patterns and brain activity during sleep emerge already early in the disease, suggesting that these alterations could be a valuable marker to detect AD in early stages. On the other hand, poor sleep quality is known to speed up disease progression, The Locus Coeruleus (LC), a key brain area controlling sleep, is affected early in AD. However, it is unclear how this impairment impacts sleep quality and brain activity. In this study, we will combine EEG, sleep analysis, functional MRI, and manipulation of LC activity in a rat model for AD to investigate how hyperactivity of the LC affects sleep patterns and whole brain activity, and whether lowering of LC activity improves sleep quality. This research may open doors to early AD detection and new preventative strategies focused on sleep.Researcher(s)
- Promoter: van den Berg Monica
Research team(s)
Project type(s)
- Research Project