WP4: Dissecting the mechanism through which the metabolite(s) modulate brain function
The hypothesis is that the chronic administration of the metabolite(s) will recapitulate core alterations seen in AD patients including behavioural disturbances, neuroinflammation, altered white matter structure and disruption of neuronal plasticity (or protective effect in case of a metabolite associated with resilience).
P3 will use a combination of in vitro and in vivo approaches to study the effect of identified metabolite(s) on behaviour, neuroinflammation and neuroplasticity (primary outcome). Then, by using transgenic mouse or pharmacological approach, we will seek cellular and molecular targets of the metabolite(s) (secondary outcome).
Overall, this WP will decipher whether and how the metabolite(s) modulate 1) behaviour 2) brain morphology (cell and synaptic density, myelination) 3) neurotransmission 4) neuroinflammation and microglia function.
Task 4.1 In vivo characterization of the effect of identified metabolite(s) on behaviour and brain functions.
Task 4.2 Ex vivo characterization of the effect of identified metabolite(s) on neuronal plasticity.
Task 4.3 In vitro characterization of the effect of identified metabolite(s) on neuroinflammatory processes.
Task 4.4 Proving cellular and molecular mechanism in vivo.