Stephan Missault staff member

Research Stephan Missault

Research team

Expertise

Stephan Missault is a neuroscientist with expertise in animal models of neurodegenerative (traumatic brain injury, epilepsy, Alzheimer) and neurodevelopmental (maternal/prenatal immune activation) disorders, with a focus on the investigation of noninvasive in vivo imaging biomarkers (MRI, PET) and novel neuromodulatory therapies.

Cholinergic and noradrenergic neuromodulation of memory and mood. 01/04/2020 - 31/03/2021

Abstract

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and whole-brain functional connectivity and cerebral blood flow in a promising rat model for Alzheimer's disease. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Cholinergic and noradrenergic modulation of memory and mood. 01/10/2018 - 30/09/2021

Abstract

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and different brain network properties in a promising AD rat model and in healthy rats. We will look at functional connectivity in the brain, oscillations in local field potentials in hippocampus (which reflect local hippocampal network properties), and whole-brain activity state related to sharp-wave ripples, a neuronal event that occurs within hippocampus and that is associated with memory. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

The role of the extracellular matrix proteases MMP-9 and uPA in the development of posttraumatic epilepsy following traumatic brain injury. 01/10/2015 - 30/09/2017

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

The role of the extracellular matrix proteases MMP-9 and uPA in the development of posttraumatic epilepsy following traumatic brain injury. 01/10/2013 - 30/09/2015

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project