Translational studies of local and systemic immune responses in epilepsy and Parkinson's disease

Projekt: Avhandling



Neuroinflammation is a feature of many neurological disorders, including Parkinson?s disease (PD) and epilepsy. Although inflammatory responses were reported decades ago in PD and epilepsy, the impact of inflammation on disease risk and outcome is still unclear. This project will study local and systemic immune responses in rodent models for PD and epilepsy with the aim of identifying immune modulatory mechanism in the respective diseases.

PD is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), intracellular accumulation of alpha-synuclein protein, microglial activation and MHCII expression. Clinically, the disease is manifested with both motor (bradykinesia, tremor, postural instability) and non-motor (sleep disturbance, gastrointestinal problems, anosmia, cognitive decline) symptoms. Many of the genes responsible for familial PD as well as genes associated to idiopathic PD are connected to immune responses, pointing out the importance of immunogenetics in PD etiology.

Epilepsy manifests as spontaneous epileptic seizures, ie abnormal synchronized activity in groups of neurons, associated with a plethoria of abruptly initiated stereotypical clinical symptoms. About 1% of the population has epilepsy and 30% are therapy resistant to current medical treatment. Most neurological disorders are associated with an increase risk of developing epilepsy, but still less is known about which pathophysiological mechanisms are directly related to the susceptibility of developing spontaneous seizures (epileptogenesis). However, there is a strong correlation between inflammatory reactions in the brain and the development of epilepsy. In addition, epileptic seizures per se induce an immune response both in the brain and systemically. The immune system may consist of new therapeutic targets for pro-active treatment during epileptogenesis.
Gällande start-/slutdatum2020/02/01 → …

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