Alzheimer’s disease & Synaptic Plasticity

 

Age- and inflammation-mediated cognitive impairment 

Several cytokines and chemokines, such as IL-1β, IL-6, TNF-α and Fractalkine, are upregulated in the hippocampus following spatial learning and exert neuromodulatory effects on both basal synaptic transmission and long-term potentiation (LTP).

We aim to better understand the molecular and electrophysiological underpinnings of learning & memory, hippocampal synaptic plasticity and the role of neuron-glia communication in these processes.

By understanding the physiological role of cytokines in memory formation and synaptic plasticity, we hope to drive the discovery of more targeted therapeutics for age-related memory impairment and Alzheimer’s disease-associated dementia. 

 

FIGURE 1: Organotypic Hippocampal Slice Culture loaded with Fluo4-AM calcium indicator and electrically-stimulated using a theta-burst protocol in the stratum moleculare of the Dentate Gyrus

 

 

In Alzheimer’s disease (AD), neurodegeneration can trigger chronic inflammation in affected brain regions. This leads to microglial and astrocyte activation and disrupts neuron-glial communication, contributing to disease progression.

We study how chronic glial cell activation can lead to dysfunctions in neuronal signalling. The aim is to identify lead compounds and develop novel targeted therapeutics for neuroinflammatory and neurodegenerative CNS disorders.

 

FIGURE 2: GFAP-labelled Astrocytes
 

 

FIGURE 3: Glial Calcium Signalling