Brain development, repair and ageing

Leader

Co-Leaders

Research center

9 Quai Saint-Bernard Université Pierre et Marie Curie, Campus Jussieu, Bâtiments A-B-C
75005 Paris
Michel Labouesse

Institution

UPMC
CNRS
ED3C 158
Université Pierre et Marie Curie

Laboratory

Biological Adaptation and Ageing
UMR8256
LabEx Biopsy, Udex Super de l'UPMC, DHU FAST

Mots clefs

Alzheimer's disease
synaptic development
post-lesion repair
non-invasive brain stimulation
Available to host a PhD student

publications

Grehl S, Martina D, Goyenvalle C, Deng ZD, Rodger J, Sherrard RM. In vitro Magnetic Stimulation: A Simple Stimulation Device to Deliver Defined Low Intensity Electromagnetic Fields. Front Neural Circuits. 2016 Nov 3;10:85. 

Vernet-der Garabedian B#, Derer P#, Bailly Y, Mariani J# (2013) Innate immunity in the Grid2Lc/+ mouse model of cerebellar neurodegeneration: glial CD95/CD95L plays a non-apoptotic role in persistent neuron loss-associated inflammatory reactions in the cerebellum J Neuroinflamm.;10:65.

Chen XR Heck N Lohof AM# Rochefort C Morel MP Wehrle R Doulazmi M# Marty S Cannaya V Avci HX# Mariani J# Rondi-Reig L Vodjdani G Sherrard RM# Sotelo C Dusart I (2013) Mature Purkinje cells require RORalpha to maintain climbing fiber mono-innervation and other adult characteristics. J Neurosci. 33(22):9546-62.

Makowiecki K, Harvey AR, Sherrard RM#, Rodger J (2014) Low-Intensity Repetitive Transcranial Magnetic Stimulation Improves Abnormal Visual Cortical Circuit Topography and Upregulates BDNF in Mice. J Neurosci 34:10780-10792

Grehl S#, Viola H, Fuller-Carter PI, Carter KW, Dunlop SA, Hool L, Sherrard RM*#, Rodger J*# (2015) Cellular and molecular changes to cortical neurons following low intensity repetitive magnetic stimulation at different frequencies. Brain Stim 8:114-123 *=co-senior

Cifuentes D, Poittevin M, Dere E#, Broqueres-You, D, Bonnin P, Benessiano J, Pocard M, Mariani J#, Kubis N, Merkulova-Rainon T, Lévy B (2014) Hypertension accelerates the progression of Alzheimer-Like pathology in a mouse model of the disease. Hypertension, (Oct 20)

Fields of research

Neurogenetics / neurodevelopment

Research Theme

BDRA studies mechanisms underlying the development, repair and ageing of the brain, using cerebellar and hippocampal models in vivo and in vitro, to address fundamental biological bases of these phenomena and to explore clinical applications.

The team’s multidisciplinary approach, from molecules to behavior and bench to the clinic, expands the Unit’s research fields into the evolution of accumulating synaptic dysfunction with time and the potential for its repair.

We are studying genes and signaling pathways that allow selective synapse stabilization during olivocerebellar development and promote appropriate post-lesion repair. We also examine the formation, maintenance and disruption of homeostatic synaptic plasticity, which is necessary to maintain functional stability in neural circuits while allowing their flexibility. Finally, we investigate the roles of different proteins associated with Alzheimer’s disease to understand early hippocampal synaptic dysfunction during this age-related pathology.

In addition we are applying our understanding of neural circuit function, stability and repair to develop translational approachs. First we are building on our expertise in non-invasive psychomotor and rTMS brain stimulation to optimize maintenance, protection and repair of synaptic circuits in the damaged or ageing brain. Second, we are applying a new complete test of cognitive function, in particular episodic memory, to ageing patients in order to provide earlier diagnosis of cognitive dysfunction, thus allowing early therapeutic intervention.





Membres de l'équipe

Ann LOHOF
Laurence CATHALA
Kiyoka KINUGAWA
Catherine ROVIRA
Béatrice VERNET-DER GARABADIAN
Hadi ZANJANI

Lab rotation

Mechanisms of non-invasive brain stimulation for neural circuit repair

Chercheur responsable: 

SHERRARD Rachel

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

~ April-June 2018 (to be discussed)

Project

Non-invasive brain stimulation such as by repetitive magnetic stimulation (rMS) can modify neural circuit function and shows promise in treating a range of neurological disorders including injury and stroke. Our team has recently shown that a low intensity rMS, which is below depolarization threshold, can improve complex learned and reflex behaviors by removing abnormal ectopic neural connections, altering neuronal morphology (spines and dendritic branching) and modifying gene expression. We are interested in how this non-depolarizing rMS induces such profound effects: what intracellular signaling paths (eg calcium) are changed?  Does the brain contain magnetoreceptors?  The project will use an in vitro organotypic model of axonal injury to identify molecular mechanisms underlying different rMS protocols, including the requirement for potential magnetoreceptors. 

Contact

Institut de Biologie Paris Seine - Bat B 4th floor, 9 Quai St Bernard 75005 Paris - +33 1 44 27 33 78 ; +33 1 44 27 32 40 - Rachel.sherrard@upmc.fr

Superviseur: 

SHERRARD Rachel & DUFOR Tom

Non-invasive brain stimulation for treating Alzheimer’s disease

Chercheur responsable: 

SHERRARD Rachel

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017 (to be discussed)

~ Jan-March 2018

~ April-June 2018

Project

Since pharmaceutical treatments for AD provide little or no benefit, and non-invasive brain stimulation (NIBS) modifies neural circuit function and improves cognitive impairment, this project will use a mouse model of AD to identify NIBS parameters that improve learning and memory as well as reduce underlying cellular pathology.  The project will particularly focus on the expression of molecular markers associated with Alzheimer’s pathology and whether NIBS improves their abnormalities.

Contact

Institut de Biologie Paris Seine - Bat B 4th floor, 9 Quai St Bernard 75005 Paris - +33 1 44 27 33 78 ; +33 1 44 27 32 40 - kiyoka.kinugawa@aphp.fr 

Superviseur: 

KINUGAWA K. & SHERRARD R.

Neuronal information processing in cerebellar microcircuit

Chercheur responsable: 

SHERRARD Rachel

Dates: 

18 September 2017 - 30 March 2018

Date limite de candidature: 

30 March 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

Project

Understanding how a neuron transforms synaptic inputs into a neuronal output is fundamental to understand information processing in the brain since neuronal circuits that mediate brain functions are formed by synapses and dysfunctions in neuronal transfer function are associated with several neurodevelopmental disorders. In our lab we are studying how information is processed by interneurons within the cerebellar microcircuit, using a multidisciplinary approach combining electrophysiological recording in vitro, 3D morphological analysis and neuronal simulation. The lab project will focus on the cellular mechanisms allowing cerebellar molecular layer interneurons to acquire their mature phenotype by studying the development of excitatory synaptic transmission and integration and its impact on information transfer. 

Contact

Institut de Biologie Paris Seine - Bat B 4th floor, 9 Quai St Bernard 75005 Paris - +33 1 44 27 32 27 - Laurence.cathala@upmc.fr

Superviseur: 

CATHALA Laurence