Cyrille Vaillend Team

Cognition, Plasticity and Neuropathologies

In brief

Our team investigates the molecular and cellular mechanisms responsible for cognitive dysfunction in neurodevelopmental (Intellectual Disability, Coffin-Lowry Syndrome, Duchenne muscular dystrophy) and neurodegenerative diseases (Alzheimer). Our multidisciplinary approach in rodent models is complemented by preclinical explorations of treatments induced by environmental modifications, pharmacological and gene therapies.

Our research

Our research is based on an integrative, multi-scale and translational approach aimed at
(1) refining our understanding of the molecular and cellular mechanisms underlying brain plasticity and cognitive processes,
(2) identifying the multiple determinants and risk factors (genetic, developmental, metabolic) that contribute to their deterioration and drive neuronal network dysfunction in animal models of neurodevelopmental (Intellectual Disability, Coffin-Lowry Syndrome, Duchenne muscular dystrophy) and neurodegenerative diseases (Alzheimer’s disease) and
(3) exploring the potential of genetic, pharmacological and behavioral rescue strategies holding realistic prospects for therapeutic perspectives. This research program capitalizes on our expertise in plasticity and cognition mechanisms to dissect the brain functional organization and neuronal mechanisms underlying high-level functions (cognition, emotion, executive functions) that go awry in these pathologies. Our multidisciplinary approach is based on classical and new rodent models and encompass behavioral studies (motor, emotional, cognitive, social and executive functions), characterization of brain plasticity (synaptic and structural plasticity, adult neurogenesis) and of multiple determinants contributing to these diseases, such as the neurogenetic, developmental, non-neuronal (glial, vascular) and metabolic factors, complemented with in vivo brain imaging, biochemistry and cell signaling, confocal imaging, molecular biology, neurosurgery, gene therapy, pharmacology… Our projects are in framed within a highly collaborative international context that includes interactions with clinicians.

Selected Publications

> Castillon C, Gonzalez L, Dominichini F, Guyon S, Da Silva K, Durand C, Lestaevel P, Vaillend C, Laroche S, Barnier JV, Poirier R. The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis. Human Molecular Genetics. 2020 Jan 16. pii: ddz296.

> Su M, Naderi K, Samson N, Youssef I, Fülöp L, Bozso Z, Laroche S, Delatour B, Davis S. Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology. Mol Neurobiol. 2019 Jan 25.

> Chaalal A, Poirier R, Blum D, Laroche S, Enderlin V (2019) Thyroid hormone supplementation restores spatial memory, hippocampal markers of neuroinflammation, plasticity-related signalling molecules and b-amyloid peptide load in hypothyroid rats. Mol Neurobiol, 56(1):722-735.

> Vaillend C, Chaussenot R. (2017) Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice. Hum Mol Genet, 26(6):1041-1055.

> Goyenvalle A, Griffith G, Babbs A, El Andaloussi S, Ezzat K, Avril A, Dugovic B, Chaussenot R, Ferry A, Voit T, Amthor H, Bühr C, Schürch S, Wood MJ, Davies KE, Vaillend C, Leumann C, Garcia L. (2015) Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat Med. 21(3):270-5.

Team members