Parkinson’s disease (PD) is the second most common neurodegenerative disease with high burden on patients, but lack of disease modifying treatment. Therefore, identification of a cause for initiation and progression of this disease are research priorities. It is widely accepted, that the pathogenic aggregation of the alpha synuclein (aSyn) protein is involved in the loss of dopaminergic neurons in PD. In this project, we aim to illuminate the influence of hypoxia on the progression and initiation of PD in a murine model with focus on inflammation. Activity and differentiation of immune cells is altered by hypoxia in tissue, and hypoxia was previously shown to contribute to neurological diseases. Since the brain is known to be a hypoxic environment, we hypothesize that aSyn pathology and the resident hypoxia pathways influence each other, thereby altering the resident immune repertoire. We will analyze the immune cells’ composition at the early differentiation stage in an animal model displaying aSyn pathology (line 61) and characterize alterations of neuronal activity in primary neuronal cultures from these mice w/wo hypoxia. Additionally, we are not only investigating the brain, but are incorporating the body of the mice to assess inflammatory processes in relationship to hypoxia pathways systemically, allowing assumptions regarding the spread, perpetuation and initiation of PD from the brain to the gut and vice versa. Currently, we are establishing a chemical hypoxia model in primary neuron culture and immortalized human cell lines. Concomitantly, we are investigating the immune cells and inflammation milieu in these mice.