Sussex Neuroscience

Dr Alessandro Colasanti

AlessandroRole of brain mitochondrial function and oxygen metabolism in the pathophysiology of mood disorders

BSMS

The human brain consumes an exceptionally high amount of energy derived from oxidative phosphorylation at the level of brain mitochondria, the cellular energy factories. Neural activities underlying most complex cognitive functions, including those related to emotional and mood regulation, require that brain mitochondria function at near maximum capacity to provide abundant and uninterrupted oxidative energy supply. Multiple abnormalities have been observed in brain and peripheral cells mitochondria in people affective by severe and chronic mood disorders, such as for example Bipolar Affective Disorder, a condition characterised by swings in mood and subjective energy levels. The dysregulation of bioenergetic processes secondary to mitochondria dysfunction might contribute to an inefficient brain oxygen metabolism and impair the ability of the brain cells to cope with the high metabolic demands associated to various stressors. This in turn could contribute to neuroprogression and functional decline of affected individuals. Dr Colasanti’s research work integrates novel neuroimaging and neuropharmacology techniques to investigate therapeutic mechanisms aimed at restoring and enhancing brain mitochondria function and oxidative regulation.

Current projects include studies in patients with mood disorders, and healthy volunteers, using new MRI methods to directly assess brain oxygenation, using physiological and pharmacological challenges to experimentally manipulate the energy production of mitochondria. Also, Dr Colasanti is investigating the relationship between oxygen consumption and the complexity of brain micro-structural organisation assessed using diffusion MRI techniques. These are collaborative projects that involve expert colleagues at the Centre for Imaging Sciences at BSMS (Prof. Mara Cercignani and Iris Asslani) and at Centre for Neuroimaging Sciences at the IoPPN, King’s College (Nisha Singh, Federico Turkheimer, and Fernando Zelaya).

Dr Colasanti is also working on the hypothesis that mitochondria abnormalities in patients with Bipolar Disorder increase their vulnerability to reduction in available oxygen. This project will test whether exposure to experimental hypoxia affects the performance of metabolically demanding cognitive tasks and related brain neuronal activities and oxygen consumption, and will compare these effects in patients with Bipolar Disorder to healthy control subjects. This project will involve use of environmental hypoxic chamber, Near Infrared Spectroscopy, and EEG measures and will be a collaboration between the Laboratory of Environmental Extremes at Brighton University (Dr Neil Maxwell) and the psychophysiology lab at BSMS (Prof Hugo Critchley)

To further demonstrate the link between mitochondrial pathology and Mood Disorders, Dr Colasanti is collaborating with Dr Robert Pitceathly and Dr Enrico Bugiardini at the UCL IoN Queensquare Centre for Neuromuscular Diseases, to investigate mood symptoms of adult patients with primary mitochondrial disorders, neurometabolic diseases characterized by a genetically determined defect of oxidative phosphorylation.

Psychoneuroimmunology of mood and imaging of neuroinflammation

These projects include collaborations with Professor Neil Harrison (BSMS); Prof Mara Cercignani (CISC), Dr Marco Bozzali (Clinical Neurology, BSMS), Prof. Pietro Ghezzi (Neuropharmacology).
Previous work by Dr Colasanti (Colasanti et a., 2016) demonstrated that neuroinflammation of the hippocampus in patients with the autoimmune and neuroinflammatory condition Multiple Sclerosis, was associated to altered neural connectivity of the hippocampus and related expression of depressive symptoms. Future work in patients with Multiple Sclerosis will integrate quantitative assessment of neuroinflammatory activity using microglia—targeting PET with novel high resolution diffusion MRI techniques to investigate in details the link between neuroinflammation and microstructural alterations of the hippocampus.

A parallel project focuses on the development of experimental neuroimaging paradigms that could be used as biomarkers of acute brain immune responses. The work includes testing the effect of glucocorticoids and acute pro-inflammatory stimuli on the expression of immune biomarkers of inflammation, both in vivo and in vitro. This work aims to further the understanding of the complex interactions between stress and brain inflammation that are critical to investigate etiopathophysiology and therapeutic mechanisms relevant for mood and other stress-related disorders.

Immunopsychiatry Clinical Research

Dr Colasanti co-leads with Prof Harrison the Immunopsychiatry research clinic at Sussex Partnership NHS Foundation Trust. The research clinic focuses on assessment and treatment of patients with treatment-resistant mood disorders and comorbid inflammation, and allows the possibility of exploratory clinical research work to better understand the effects of personalised immunomodulating treatments for patients with mood disorders that are not sufficiently improving with conventional treatments.