Anxiolytic and anti-epileptogenic roles of brain protease-activated receptor (PAR2) [ 2007 - 2009 ]

Research Grant

Researchers: A/Pr Thomas Cocks (Principal investigator) ,  Prof Maarten Van Den Buuse ,  Prof Terence O'Brien

Brief description Epilepsy and anxiety are two of the most common chronic brain conditions world-wide, affecting hundreds of millions people worldwide, and are associated with a considerable burden of disability, impaired quality of life, a range of co-morbidities (eg physical injury, psychiatric disorder) and premature death. People who develop epilepsy have often experienced an initial insult (e.g. head trauma, brain inflammation, febrile convulsions) and then live for months to years before seizures develop. This latent period between the initial insult and the onset of recurrent seizures is referred to as epileptogenesis - the transformation of the brain from the non-epileptic to the epileptic state in which a vicious cycle develops where 'seizures beget seizures.' This process cannot currently be prevented once it begins. A similar process has been implicated in the development of chronic anxiety, with an initial early life brain insult or stress and the emergence of the condition later in life. There are no treatments to prevent or cure either disease, only drugs to alleviate the symptoms. We, however, have now discovered that a small protein, called, SLIGRL that activates cell detector molecules called PAR2 which are involved in controlling brain inflammation, inhibits epileptogenesis and anxiety in well-defined rodent models. In the experiments outlined in this grant, we will confirm these very exciting preliminary findings in other models of epileptogenesis and anxiety, as well as determine the underlying mechanisms of the protection. We will also examine if SLIGRL helps prevent a peripheral inflammatory diseases - colitis - by an anti-inflammatory action in the brain similar. The main outcome of our study will be important proof-of-principle data for the development of drugs like SLIGRL for clinical use for the treatment of epilepsy, anxiety and possibly other brain diseases where inflammation plays an important role.

Funding Amount $AUD 262,073.37

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant