| dc.description.abstract | Bipolar disorder (BPD), also known as manic depressive illness, is a complex brain disorder common under adults as well as adolescents. Patients with BPD disorder suffer from dramatic mood swings, which severely hamper a patient’s life. Symptoms vary from hyperactivity and psychosis during mania to self-deprecatory and anxious behaviour during depression. These contrasting symptoms hinder the search for a cause and treatment for BPD. Currently used medicines are often anti-depressants with many unwanted side effects, and of which the exact working mechanism are unclear. Therefore, there is a need for a specific treatment for BPD. Recent studies with knockout mice pointed at the enzyme adenylyl cyclase subtype 8 as potential treatment target for BPD, but further research has to confirm this. In this thesis, the potential of different adenylyl cyclase subtypes as treatment targets for BPD is studied. This is approached by studying the BPD symptoms and their underlying molecular mechanisms, and by linking characteristics of adenylyl cyclase subtypes to BPD symptoms. These approaches lead to the finding that adenylyl cyclase subtype 1 and adenylyl cyclase subtype 8 play an important role in BPD pathology. This is shown by their role in neural growth and other neural processes, their expression in the cerebellum and hypothalamus, and their involvement in the hypothalamic-pituitary- adrenal -axis. In addition, AC8 is crucial for the generation of behavioural stress responses, and it induces anti-depressive or manic like behaviour. Furthermore, the findings in this thesis indicate a major amplifying role for anxiety in the development and course of BPD. Also anxiety generation involves AC1 and AC8, which supports the strong relation between anxiety and BPD. Taken together, these results point at anxiety, AC1 and AC8 as high potential treatment targets for BPD. | |
