PhD: Vincent Maingret

Modulation of synaptic plasticity by PGE2 at mossy fiber/CA3 synapse in physiological condition and in a mouse model of Alzheimer disease

Defended on December 12, 2014

Alzheimer’s disease (AD) is the most common form of dementia in elder people characterized by a loss of cognitive function linked to synaptic deficits. There is considerable evidence that neuroinflammation and AD are intimately linked.

The key role of neuroinflammation in the course of the disease was figured out by epidemiological studies reporting a reduced prevalence to develop AD for patients chronically treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Prostaglandins are lipidic mediators derived from arachidonic acid and their synthesis is inhibited by NSAIDs. Among prostaglandins, PGE2 is known to modulate synaptic transmission and plasticity in the hippocampus and its concentration is higher in brains from AD patients. Numerous studies have reported synaptic deficits in the course of AD, mainly in the hippocampus which is essential for cognitive functions like learning or memory formation.

The vast majority of these studies were focused on postsynaptic deficits at the canonical CA3-CA1 synapse. On the opposite, the synapse between mossy fiber and CA3 pyramidal cell (Mf-CA3) that express presynaptic short-term and long-term plasticity, was poorly studied in the context of AD. The aim of my project was to decipher the involvement of PGE2 in synaptic deficits in a mouse model of AD, the APPswe/PS1ΔE9 (APP/PS1).

Our results show that acute application of PGE2 on wild type young mice impairs only presynaptic long term potentiation (LTP) at the Mf-CA3 synapse via the specific activation of EP3 receptor. In APP/PS1 mice, we demonstrate that the sole deficit at the Mf-CA3 synapse is an impairment of the presynaptic LTP at 12 months of age.

Finally we demonstrate that the impaired presynaptic LTP in APP/PS1 mice can be rescued by the acute application of a specific EP3 receptor antagonist, pointing out the key role of PGE2 – EP3 signaling pathway in synaptic deficits in hippocampus in a mouse model of AD.

Keywords: hippocampus, mossy fiber, presynaptic LTP, PGE2, Alzheimer’s disease, synaptic plasticity


Blockade of EP3 receptor rescues deficits in synaptic plasticity at hippocampal mossy fiber synapses in APPswe/PS1DE9 mouse model of Alzheimer’s disease (in preparation)

Vincent Maingret1,2, Séverine Deforges1,2, Christophe Mulle1,2 and Thierry Amédée1,2*
1Interdisciplinary Institute for Neuroscience, CNRS UMR 5297
University of Bordeaux, F-33000 Bordeaux, France


  • OLIET, Stéphane
    DR CNRS  – Chairman
  • MARIE, Hélène 
    DR CNRS  – Reviewer
  • GIAUME, Christian 
    DR CNRS  – Reviewer
  • CHO, Yoon 
    MC Université Bordeaux  – Examiner
    MALLAT, Michel 
    DR INSERM  – Examiner
    AMEDEE, Thierry 
    DR CNRS  – thesis supervisor

Thesis supervisor

Thierry Amédée
Directeur de recherche – PhD
Institut interdisciplinaire de Neurosciences
Team  Physiology of glutamatergic synapses

Last update: 12 December 2014