Janssen M. Kotah

I am a Filipino neuroscientist currently based in the Netherlands. My PhD work with the Aniko Korosi and Paul Lucassen lab at the University of Amsterdam involved the use of mouse models to study long term consequences of early-life stress exposure on later-life challanges, such as aging, inflammation, and amyloid-β neuropathology. I am currently a postdoc in the lab of prof. dr. Bart Eggen, studying microglial profiles in the context of neurodegenerative conditions such as Alzheimer's disease and multiple sclerosis.

While my bachelors degree was in psychology, during my masters in the Neurasmus program, I was able to acquire a more neurobiological background. During my PhD, I was able to supplement this with a variety of wet lab experiments involving behavioral neuroscience and molecular neurobiology. Currently, I am doing a more bioinformatics-focused postdoc, as I use single cell and spatial transcriptomic approaches to study the human brain.

My hope is to someday use this combination of wet and dry lab skills to contribute to building neuroscience in the Philippines.

selected publications

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions

Kitty Reemst, Laura Kracht, Janssen M. Kotah, Reza Rahimian, Astrid A.S. Irsen, Gonzalo Congrains Sotomayor, Laura N. Verboon, Nieske Brouwer, Sophie Simard, Gustavo Turecki, Naguib Mechawar, Susanne M. Kooistra, Bart J.L. Eggen, and Aniko Korosi

Translational psychiatry, Dec 2022

*Reemst K, Kracht L, Kotah JM, and Rahimian R contributed equally

Abs DOI

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS-induced by limited bedding and nesting material during the first week of life (postnatal days [P]2–9) on microglial (i) morphology; (ii) hippocampal gene expression; and (iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to control microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis

Astrid M. Alsema, Marion H. C. Wijering, Anneke Miedema, Janssen M. Kotah, Mirjam Koster, Merel Rijnsburger, Hilmar R. J. Weering, Helga E. Vries, Wia Baron, Susanne M. Kooistra, and Bart J. L. Eggen

Nat Neurosci, Nov 2024

*Alsema AM, Wijering MHC, Miedema A, and Kotah JM contributed equally

Abs DOI

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions. Expression changes in astrocyte-specific, oligodendrocyte-specific and microglia-specific gene sets characterize the active lesion rims. Furthermore, we identify three WM lesion progression trajectories, predicting how normal-appearing WM can develop into WM active or mixed active-inactive lesions. Our data shed light on the dynamic progression of MS lesions.
Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism

Janssen M. Kotah, Mandy S. J. Kater, Niek Brosens, Sylvie L. Lesuis, Roberta Tandari, Thomas M. Blok, Luca Marchetto, Ella Yusaf, Frank T. W. Koopmans, August B. Smit, Paul J. Lucassen, Harm J. Krugers, Mark H. G. Verheijen, and Aniko Korosi

Alzheimers Dement, Mar 2024

*Kotah JM and Kater MSJ contributed equally

Abs DOI

INTRODUCTION: Early-life stress (ES) increases the risk for Alzheimer’s disease (AD). We and others have shown that ES aggravates amyloid-beta (Aβ) pathology and promotes cognitive dysfunction in APP/PS1 mice, but underlying mechanisms remain unclear. METHODS: We studied how ES affects the hippocampal synaptic proteome in wild-type (WT) and APP/PS1 mice at early and late pathological stages, and validated hits using electron microscopy and immunofluorescence. RESULTS: The hippocampal synaptosomes of both ES-exposed WT and early-stage APP/PS1 mice showed a relative decrease in actin dynamics-related proteins and a relative increase in mitochondrial proteins. ES had minimal effects on older WT mice, while strongly affecting the synaptic proteome of advanced stage APP/PS1 mice, particularly the expression of astrocytic and mitochondrial proteins. DISCUSSION: Our data show that ES and amyloidosis share pathogenic pathways involving synaptic mitochondrial dysfunction and lipid metabolism, which may underlie the observed impact of ES on the trajectory of AD.