DrBruna Panizzutti Parry

Knowledge Areas
Mental Health
Drug Repurposing
Stem cell In vitro models
Molecular Biology
Mitochondria

Projects
1) Bipolar disorder is a top 10 cause of disability worldwide, yet it is more poorly resourced in research and treatment options than any other major
cause of disability. The development of new treatments has stagnated due to a lack of knowledge of the underlying neuropathophysiological mechanisms involved in the disease. We have bypassed this obstacle using an entirely novel cross-disciplinary approach by employing an in vitro model system that retains the genetic characteristics of the patient and allows access to relevant cells and processes, to 1) identify new treatment options for bipolar disorder that will improve medical outcomes; 2) further investigate the mechanisms involved in the pathophysiology of the disease. 

2)Alterations in multiple biological systems have been observed in people with bipolar disorder, with immune dysfunction recognised as an important mechanism. Inflammatory and immunity-related mechanisms have been investigated to understand their contribution to disease progression and treatment effectiveness. In the central nervous system, microglial cells perform various functions such as phagocytosing apoptotic neurons, inducing neuronal apoptosis, synaptic pruning, synapse formation, promoting pyramidal neuron survival, regulating receptor expression at synapses, controlling the production and migration of cortical inhibitory neurons, inflammatory response. Microglial cells can be polarised into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes responding to different cytokines. Activation of microglia and neuroinflammation have been implicated in neuropsychiatric disorders like schizophrenia, major depressive disorder, and bipolar disorder.

3) People with bipolar disorder have a high death rate by suicide and self-harm. Lithium is commonly prescribed to minimise bipolar disorder symptoms effectively. However, lithium is only fully effective in 20% of the patients and its molecular mechanisms remain unknown. Studies have shown that bipolar disorder is partly due to dysregulated adenosine triphosphate (energy) generation machinery and lithium could have positive impact on mitochondria-related genes. Mitochondria are essential for cellular energy production, but their role in bipolar disorder and how their function will be affected by lithium treatment have not been determined.