Assoc ProfessorDerek Costello

Most neurodegenerative conditions, including Alzheimer's disease and age-related cognitive decline, are associated with inflammatory changes in the brain. The complex interaction between neuronal circuitry, the resident immune cells of the brain and the systemic immune system becomes disrupted in these disease states. This leads to progressive impairment in brain function. Our work examines the physiological mechanisms which underlie dysfunction of learning and memory under disease conditions. We use a multi-disciplinary approach to investigate the regulation of immune response in the brain, and its impact upon neuronal function. We also assess the potential for immunomodulatory and anti-inflammatory agents to restore function under inflammatory conditions.

Some members of society are more vulnerable to neurodegenerative disease. These include individuals with metabolic disorders, prior brain injuries and other chronic inflammatory conditions. We aim to understand the cellular mechanisms that promote susceptibility, and interrogate potential therapeutic strategies to alleviate this risk. Our work has illustrated that harnessing the benefits of the endogenous immuno-protective mechanisms of the brain may provide a potential avenue for therapeutic intervention into inflammatory-related neurodegenerative disease.

Experimental Techniques:
Electrophysiology ( in vitro ) - Extracellular and whole-cell patch-clamp recording from acute and cultured brain slices (including knockout and transgenic animals) and primary cultured neurons
Biochemical analyses - including Western immunoblot assay, enzyme-linked immunosorbent assay, cellular toxicity analysis and real-time PCR analysis

Imaging analysis - Live-cell, 2-photon fluorescent microscopy on brain slices and primary neuronal cultures (including simultaneous patch-clamp recording)
Behavioural analyses - Analysis of hippocampal-dependent learning
Biological preparations - Acute and organotypic hippocampal slices, cultured cell lines, primary neuronal cultures, primary microglial and astrocytic cultures, macrophages.

Model organisms - zebrafish larvae as in vivo models of inflammatory and neurological dysfunction.