Non-motor symptoms and complications in Parkinson´s disease: modeling and identification of targets for therapy

The goal of this Research Project is to study non-motor symptoms associated with Parkinson’s disease (PD) and whith complications caused by dopamine replacement therapies.

Psychiatric and sleep-related comorbidities are frequently observed in PD and are a major factor affecting the patients’ quality of life, since they are often refractory to standard medications used to treat the cardinal motor symptoms.

We have developed experimental models of PD, which reproduce several non-motor symptoms, including sleep disorders, and affective and cognitive deficits.

We have also been able to mimic addictive-like and obsessive compulsive responses to L-Dopa and dopamine receptor agonists, such us pramipexole.

We will combine the use of these models with electrophysiological, advanced optical imaging and behavioral analyses to better understand these pathological conditions.

In particular, we will investigate mechanisms underlying excessive daytime sleepiness, and sleep fragmentation, as well as memory deficits, depression and anxiety.

Pharmacological and transgenic interventions targeting components of dopaminergic, noradrenergic and serotonergic systems, including the dorsal raphe nucleus, locus coeruleus and forebrain structures, will be examined for their ability to counteract specific comorbidities.

In parallel studies, we will also investigate the molecular abnormalities at the basis of psychiatric complications associated with administration of L-DOPA and dopamine agonists.