Search

Your search keyword '"D'Hooge, Rudi"' showing total 937 results
Start Over Author "D'Hooge, Rudi"
937 results on '"D'Hooge, Rudi"'

153. Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

Author

Eisch Amelia, Cremer Harold, Reumers Veerle, Baekelandt Veerle, Moons Michaël, Antonucci Flavia, Cremer Jonathan, DeVriese Astrid, D'Hooge Rudi, Balschun Detlef, Ahmed Tariq, Coremans Vanessa, Lagace Diane, Janssens Tom, Bozzi Yuri, Caleo Matteo, and Conway Edward M

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

Published
2010
Full Text
View/download PDF

157. Aged Tmem106b knockout mice display gait deficits in coincidence with Purkinje cell loss and only limited signs of non‐motor dysfunction.

Author

Stroobants, Stijn, D'Hooge, Rudi, and Damme, Markus

Subjects
*PURKINJE cells, *KNOCKOUT mice, *CENTRAL nervous system, *COGNITIVE ability, *BRAIN stem, *COINCIDENCE, *NEUROPSYCHOLOGICAL tests, *LYSOSOMES
Abstract

Genetic variants in TMEM106B are a major risk factor for several neurodegenerative diseases including frontotemporal degeneration, limbic‐predominant age‐related TDP‐43 encephalopathy, Parkinson's disease, late‐onset‐Alzheimer's disease and constitute a genetic determinant of differential aging. TMEM106B encodes an integral lysosomal membrane protein but its precise physiological function in the central nervous system remains enigmatic. Presently, we aimed to increase understanding of TMEM106B contribution to general brain function and aging. We analyzed an aged cohort of Tmem106b knockout‐, heterozygote and wild‐type mice in a behavioral test battery including assessments of motor function as well as, social, emotional and cognitive function. Aged Tmem106b knockout (KO) mice displayed diverse behavioral deficits including motor impairment, gait defects and reduced startle reactivity. In contrast, no prominent deficits were observed in social, emotional or cognitive behaviors. Histologically, we observed late‐onset loss of Purkinje cells followed by reactive gliosis in the cerebellum, which likely contributed to progressive decline in motor function and gait defects in particular. Reactive gliosis was not restricted to the cerebellum but observed in different areas of the brain including the brain stem and parts of the cerebral cortex. Surviving Purkinje cells showed vacuolated lysosomes in the axon initial segment, implicating TMEM106B‐dependent lysosomal trafficking defects as the underlying cause of axonal and more general neuronal dysfunction contributing to behavioral impairments. Our experiments help to elucidate how TMEM106B affects spatial neuronal homeostasis and exemplifies a critical role of TMEM106B in neuronal cells for survival. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

160. Comparison between touchscreen operant chambers and water maze to detect early prefrontal dysfunction in mice.

Author

Van den Broeck, Lore, Sierksma, Annerieke, Hansquine, Pierre, Thonnard, David, Callaerts‐Vegh, Zsuzsanna, and D'Hooge, Rudi

Subjects
TOUCH screens, MAZE tests, MICE, NEUROPLASTICITY, ALZHEIMER'S disease, SHORT-term memory
Abstract

The relative lack of sensitive and clinically valid tests of rodent behavior might be one of the reasons for the limited success of the clinical translation of preclinical Alzheimer's disease (AD) research findings. There is a general interest in innovative behavioral methodology, and protocols have been proposed for touchscreen operant chambers that might be superior to existing cognitive assessment methods. We assessed and analyzed touchscreen performance in several novel ways to examine the possible occurrence of early signs of prefrontal (PFC) functional decline in the APP/PS1 mouse model of AD. Touchscreen learning performance was compared between APP/PS1‐21 mice and wildtype littermates on a C57BL/6J background at 3, 6 and 12 months of age in parallel to the assessment of spatial learning, memory and cognitive flexibility in the Morris water maze (MWM). We found that older mice generally needed more training sessions to complete the touchscreen protocol than younger ones. Older mice also displayed defects in MWM working memory performance, but touchscreen protocols detected functional changes beginning at 3 months of age. Histological changes in PFC of APP/PS1 mice indeed occurred as early as 3 months. Our results suggest that touchscreen operant protocols are more sensitive to PFC dysfunction, which is of relevance to the use of these tasks and devices in preclinical AD research and experimental pharmacology. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

163. PLD3 and spinocerebellar ataxia

Author

Gonzalez, Adriana Carolina, primary, Stroobants, Stijn, additional, Reisdorf, Pia, additional, Gavin, Amanda Lee, additional, Nemazee, David, additional, Schwudke, Dominik, additional, D'Hooge, Rudi, additional, Saftig, Paul, additional, and Damme, Markus, additional

Published
2018
Full Text
View/download PDF

171. Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate

Author

Woolley, Daniel G, Mantini, Dante, Coxon, James P, D'Hooge, Rudi, Swinnen, Stephan, Wenderoth, Nici, and Neurology

Subjects
Adult, Medicine(all), Brain Mapping, Caudate Nucleus/physiology, REST, Visual Perception/physiology, water, Signal Processing, Computer-Assisted, Functional Laterality, User-Computer Interface, Neural Pathways/physiology, Maze Learning/physiology, Humans, magnetic resonance imaging, young adult, Female, Cues, Hippocampus/physiology
Abstract

Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well-learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting-state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior-only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior-only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation-related processing. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc. ispartof: Human Brain Mapping vol:36 issue:4 pages:1265-77 ispartof: location:United States status: published

Published
2016
Full Text
View/download PDF

173. Testosterone boosts physical activity in male mice via dopaminergic pathways

Author

Jardí, Ferran, primary, Laurent, Michaël R., additional, Kim, Nari, additional, Khalil, Rougin, additional, De Bundel, Dimitri, additional, Van Eeckhaut, Ann, additional, Van Helleputte, Lawrence, additional, Deboel, Ludo, additional, Dubois, Vanessa, additional, Schollaert, Dieter, additional, Decallonne, Brigitte, additional, Carmeliet, Geert, additional, Van den Bosch, Ludo, additional, D’Hooge, Rudi, additional, Claessens, Frank, additional, and Vanderschueren, Dirk, additional

Published
2018
Full Text
View/download PDF

181. Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity

Author

Research Foundation - Flanders, Flanders Institute for Biotechnology, Salas, Isabel H., Callaerts-Vegh, Zsuzsanna, Arranz, Amaia M., Guix, Francesc X., D`Hooge, Rudi, Esteban, José A., Strooper, Bart de, Dotti, Carlos G., Research Foundation - Flanders, Flanders Institute for Biotechnology, Salas, Isabel H., Callaerts-Vegh, Zsuzsanna, Arranz, Amaia M., Guix, Francesc X., D`Hooge, Rudi, Esteban, José A., Strooper, Bart de, and Dotti, Carlos G.

Abstract

Tetraspanins (Tspan) are transmembrane proteins with important scaffold and signalling functions. Deletions of Tetraspanin 6 (Tspan6) gene, a member of the tetraspanin family, have been reported in patients with Epilepsy Female-restricted with Mental Retardation (EFMR). Interestingly, mutations in Tspan7, highly homologous to Tspan6, are associated with X-linked intellectual disability, suggesting that these two proteins are important for cognition. Considering recent evidences showing that Tspan7 plays a key role in synapse development and AMPAR trafficking, we initiated the study of Tspan6 in synaptic function using a Tspan6 knock out mouse model. Here we report that hippocampal field recordings from Tspan6 knock out mice show an enhanced basal synaptic transmission and impaired long term potentiation (LTP). A normal paired-pulse facilitation response suggests that Tspan6 affects the properties of the postsynaptic rather than the presynaptic terminal. However, no changes in spine morphology or postsynaptic markers could be detected in Tspan6 KO mice compared with wild types. In addition, Tspan6 KO mice show normal locomotor behaviour and no defects in hippocampus-dependent memory tests.

Published
2017

192. A2A adenosine receptor deletion is protective in a mouse model of Tauopathy

Author

Laurent, Cyril, Van Der Jeugd, Anneke, Faivre, Emilie, Flaten, Vanessa, Ledent, Catherine, D'Hooge, Rudi, Sergeant, Nicolas, Hamdane, Malika, Humez, Sandrine, Müller, C.E., Lopes, Luísa Vaqueiro, Burnouf, Sylvie, Buée, Luc, Blum, David, Ferry, Barbara, Batalha, Vânia V.L., Coelho, J.E., Baqi, Younis, Malik, Enas, Mariciniak, E., Parrot, Sandrine, Laurent, Cyril, Van Der Jeugd, Anneke, Faivre, Emilie, Flaten, Vanessa, Ledent, Catherine, D'Hooge, Rudi, Sergeant, Nicolas, Hamdane, Malika, Humez, Sandrine, Müller, C.E., Lopes, Luísa Vaqueiro, Burnouf, Sylvie, Buée, Luc, Blum, David, Ferry, Barbara, Batalha, Vânia V.L., Coelho, J.E., Baqi, Younis, Malik, Enas, Mariciniak, E., and Parrot, Sandrine

Abstract

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

194. Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis

Author

Verreet, Tine, primary, Rangarajan, Janaki Raman, additional, Quintens, Roel, additional, Verslegers, Mieke, additional, Lo, Adrian C., additional, Govaerts, Kristof, additional, Neefs, Mieke, additional, Leysen, Liselotte, additional, Baatout, Sarah, additional, Maes, Frederik, additional, Himmelreich, Uwe, additional, D'Hooge, Rudi, additional, Moons, Lieve, additional, and Benotmane, Mohammed A., additional

Published
2016
Full Text
View/download PDF

197. Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models

Author

Huang, Yunhong, Skwarek-Maruszewska, Aneta, Horré, Katrien, Vandewyer, Elke, Wolfs, Leen, Snellinx, An, Saito, Takashi, Radaelli, Enrico, Corthout, Nikky, Colombelli, Julien, Lo, Adrian C, Van Aerschot, Leen, Callaerts-Vegh, Zsuzsanna, Trabzuni, Daniah, Bossers, Koen, Verhaagen, Joost, Ryten, Mina, Munck, Sebastian, D'Hooge, Rudi, Swaab, Dick F, Hardy, John, Saido, Takaomi C, De Strooper, Bart, Thathiah, Amantha, Huang, Yunhong, Skwarek-Maruszewska, Aneta, Horré, Katrien, Vandewyer, Elke, Wolfs, Leen, Snellinx, An, Saito, Takashi, Radaelli, Enrico, Corthout, Nikky, Colombelli, Julien, Lo, Adrian C, Van Aerschot, Leen, Callaerts-Vegh, Zsuzsanna, Trabzuni, Daniah, Bossers, Koen, Verhaagen, Joost, Ryten, Mina, Munck, Sebastian, D'Hooge, Rudi, Swaab, Dick F, Hardy, John, Saido, Takaomi C, De Strooper, Bart, and Thathiah, Amantha

Published
2015

198. Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

Author

Ridder, Dirk A., Wenzel, Jan, Mueller, Kristin, Toellner, Kathrin, Tong, Xin-Kang, Assmann, Julian C., Stroobants, Stijn, Weber, Tobias, Niturad, Cristina, Fischer, Lisanne, Lembrich, Beate, Wolburg, Hartwig, Grand'Maison, Marilyn, Papadopoulos, Panayiota, Korpos, Eva, Truchetet, Francois, Rades, Dirk, Sorokin, Lydia M., Schmidt-Supprian, Marc, Bedell, Barry J., Pasparakis, Manolis, Balschun, Detlef, D'Hooge, Rudi, Loescher, Wolfgang, Hamel, Edith, Schwaninger, Markus, Ridder, Dirk A., Wenzel, Jan, Mueller, Kristin, Toellner, Kathrin, Tong, Xin-Kang, Assmann, Julian C., Stroobants, Stijn, Weber, Tobias, Niturad, Cristina, Fischer, Lisanne, Lembrich, Beate, Wolburg, Hartwig, Grand'Maison, Marilyn, Papadopoulos, Panayiota, Korpos, Eva, Truchetet, Francois, Rades, Dirk, Sorokin, Lydia M., Schmidt-Supprian, Marc, Bedell, Barry J., Pasparakis, Manolis, Balschun, Detlef, D'Hooge, Rudi, Loescher, Wolfgang, Hamel, Edith, and Schwaninger, Markus

Abstract

Inactivating mutations of the NF-kappa B essential modulator (NEMO), a key component of NF-kappa B signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood-brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-kappa B and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-kappa B-independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1-NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP.

Published
2015

199. Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

Author

Papadopoulou, Aikaterini S, Serneels, Lutgarde, Achsel, Tilmann, Mandemakers, Wim, Callaerts-Vegh, Zsuzsanna, Dooley, James, Lau, Pierre, Ayoubi, Torik, Radaelli, Enrico, Spinazzi, Marco, Neumann, Melanie, Hébert, Sébastien S, Silahtaroglu, Asli, Liston, Adrian, D'Hooge, Rudi, Glatzel, Markus, De Strooper, Bart, Papadopoulou, Aikaterini S, Serneels, Lutgarde, Achsel, Tilmann, Mandemakers, Wim, Callaerts-Vegh, Zsuzsanna, Dooley, James, Lau, Pierre, Ayoubi, Torik, Radaelli, Enrico, Spinazzi, Marco, Neumann, Melanie, Hébert, Sébastien S, Silahtaroglu, Asli, Liston, Adrian, D'Hooge, Rudi, Glatzel, Markus, and De Strooper, Bart

Abstract

miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomotor impairment and ataxia. The different members of the miR-29 family are strongly expressed in neurons of the olfactory bulb, the hippocampus and in the Purkinje cells of the cerebellum. Morphological analysis showed that Purkinje cells are smaller and display less dendritic arborisation compared to their wildtype littermates. In addition, a decreased number of parallel fibers form synapses on the Purkinje cells. We identified several mRNAs significantly up-regulated in the absence of the miR-29a/b-1 cluster. At the protein level, however, the voltage-gated potassium channel Kcnc3 (Kv3.3) was significantly up-regulated in the cerebella of the miR-29a/b knockout mice. Dysregulation of KCNC3 expression may contribute to the ataxic phenotype.

Published
2015

200. Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models

Author

Huang, Yunhong, primary, Skwarek-Maruszewska, Aneta, additional, Horré, Katrien, additional, Vandewyer, Elke, additional, Wolfs, Leen, additional, Snellinx, An, additional, Saito, Takashi, additional, Radaelli, Enrico, additional, Corthout, Nikky, additional, Colombelli, Julien, additional, Lo, Adrian C., additional, Van Aerschot, Leen, additional, Callaerts-Vegh, Zsuzsanna, additional, Trabzuni, Daniah, additional, Bossers, Koen, additional, Verhaagen, Joost, additional, Ryten, Mina, additional, Munck, Sebastian, additional, D’Hooge, Rudi, additional, Swaab, Dick F., additional, Hardy, John, additional, Saido, Takaomi C., additional, De Strooper, Bart, additional, and Thathiah, Amantha, additional

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results