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A Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders. Vrije Universiteit Brussel

Rudolf L Z Ganzoni, Sofie Bournons, Erick M Carreira, Dimitri De Bundel, Ilse Smolders

Photopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising for the treatment of neurological disorders. Despite the enticing prospects of photopharmacology, its application to treat human central nervous system (CNS) diseases remains to be demonstrated. In this review, we provide an overview of prominent ...

Interneuron migration impairment and brain region-specific DNA damage response following irradiation during early neurogenesis in mice Vrije Universiteit Brussel Universiteit Hasselt

Lisa Berden, Nicholas Rajan, André Claude Mbouombouo Mfossa, Isabeau De Bie, Emre Etlioglu, Mohammed Abderrafi Benotmane, Mieke Verslegers, Najat Aourz, Ilse Smolders, Jean-Michel Rigo, et al.

Embryonic DNA damage resulting from DNA repair deficiencies or exposure to ionizing radiation during early neurogenesis can lead to neurodevelopmental disorders, including microcephaly. This has been linked to an excessive DNA damage response in dorsal neural progenitor cells (NPCs), resulting in p53-dependent apoptosis and premature neuronal differentiation which culminates in depletion of the NPC pool. However, the effect of DNA damage on ...

Neuromedin U Neurons in the Edinger-Westphal Nucleus Respond to Alcohol Without Interfering with the Urocortin 1 Response Vrije Universiteit Brussel

Mireia Medrano, Wissal Allaoui, Ra'fat Ehab Salim Haddad, Leila Makrini-Maleville, Emmanuel Valjent, Ilse Smolders, Viktória Kormos, Balázs Gaszner, Dimitri De Bundel

The Edinger-Westphal nucleus (EW) is a midbrain nucleus composed of a preganglionic, cholinergic subpopulation and a densely clustered peptidergic subpopulation (EWcp). The EWcp is one of the few brain regions that show consistent induction of FOS following voluntary alcohol intake. Previous results in rodents point to urocortin 1 (UCN1) as one of the peptides most involved in the control of ethanol intake and preference. Notably, the ...

Regulatory T cells as a possible new target in epilepsy? Vrije Universiteit Brussel

Evelien Hendrix, Maxime Vande Vyver, Matthew Holt, Ilse Smolders
Epilepsy is a complex chronic brain disorder with diverse clinical features that can be caused by various triggering events, such as infections, head trauma, or stroke. During epileptogenesis, various abnormalities are observed, such as altered cellular homeostasis, imbalance of neurotransmitters, tissue changes, and the release of inflammatory mediators, which in combination lead to spontaneous recurrent seizures. Regulatory T cells (Tregs), a ...

Chemogenetic Approaches to Study Astrocytes at Glutamatergic Synapses Vrije Universiteit Brussel

Liam Nestor, Yana Van Den Herrewegen, Zuner A Bortolotto, Dimitri De Bundel, Ilse Smolders

Chemogenetic modulation, via the use of designer receptors exclusively activated by designer drugs (DREADDs), is an established in vivo approach that allows cell-type-specific and spatiotemporally defined modulation of the brain. It combines both a genetic and a pharmacological aspect and can be used in multiple cell types such as neurons and glia. Several DREADDs have been developed, of which the muscarinic G-protein-coupled receptor DREADDs ...

Unravelling the brain metabolome: A review of liquid chromatography - mass spectrometry strategies for extracellular brain metabolomics Vrije Universiteit Brussel

Liam Nestor, Dimitri De Bundel, Yvan Vander Heyden, Ilse Smolders, Ann Van Eeckhaut
The analysis of the brain extracellular metabolome is of interest for numerous subdomains within neuroscience. Not only does it provide information about normal physiological functions, it is even more of interest for biomarker discovery and target discovery in disease. The extracellular analysis of the brain is particularly interesting as it provides information about the release of mediators in the brain extracellular fluid to look at cellular ...

Neurofilament light chain Vrije Universiteit Brussel

Marie-Laure Custers, Maxime Vande Vyver, Lea Kaltenböck, Kurt Barbé, Maria Bjerke, Ann Van Eeckhaut, Ilse Smolders

OBJECTIVE: In the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the evaluation of treatment responsiveness. In this regard, biochemical traceability in biofluids is notably absent in contrast to other diseases. In the present preclinical study, we investigated the potential of neurofilament light chain (NfL) as a possible diagnostic ...

Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience Vrije Universiteit Brussel

Jo Bossuyt, Yana Van Den Herrewegen, Liam Nestor, An Buckinx, Dimitri De Bundel, Ilse Smolders
Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting-edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous ...

Epileptiforme activiteit bij de ziekte van Alzheimer Vrije Universiteit Brussel

Amber Nous, Maxime Vande Vyver, Ilse Smolders
In ons onderzoeksteam aan de Vrije Universiteit Brussel streven we naar een beter begrip van de rol van oplosbaar amyloïd-beta en tau eiwitten in het ontstaan van epileptische aanvallen bij de ziekte van Alzheimer. We onderzoeken dit aan de hand van Alzheimer muismodellen en mensen die zich in verschillende stadia van het Alzheimer continuüm bevinden.

Normal Pregnancy-Induced Islet Beta Cell Proliferation in Mouse Models That Are Deficient in Serotonin-Signaling Vrije Universiteit Brussel KU Leuven

Lotte Goyvaerts, Anica Schraenen, Katleen Lemaire, Peter In't Veld, Ilse Smolders, Luc Maroteaux, Frans Schuit

During mouse pregnancy placental lactogens stimulate prolactin receptors on pancreatic islet beta cells to induce expression of the tryptophan hydroxylase Tph1, resulting in the synthesis and secretion of serotonin. Presently, the functional relevance of this phenomenon is unclear. One hypothesis is that serotonin-induced activation of 5-HT2B receptors on beta cells stimulates beta cell proliferation during pregnancy. We tested this ...