Supervisors info:
Στεφανής Λεωνίδας, Καθηγητής, Ιατρική, ΕΚΠΑ
Δάλλα Χριστίνα, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Ξυλούρη Μαρία, Ερευνήτρια Δ΄, ΙΙΒΕΑ
Summary:
Parkinson's disease is a progressive neurodegenerative brain disease and more specifically the second most common one. The main symptoms of the disease which are also the main clinical signs are bradykinesia, resting tremor, stiffness and postural instability. However, these motor impairments are often accompanied by other non-motor symptoms such as sleep disorders, olfactory decline, neuropsychiatric disorders (depression, anxiety) and various cognitive disorders (attention loss, dementia).
The study of these non-motor symptoms is a highly growing field and requires particular attention due to their close association with the quality of life of patients and of course with the diagnosis. More specifically, cognitive decline, sleep disorders and depressive phenotypes, seem to particularly influence the quality of life of patients, to a greater extent than motor features, creating an even more complex picture around the disease. Moreover, it has already been known, that in many cases non-motor symptoms appear earlier than the motor ones. As a result, it is well understood that their study could effectively contribute to the early diagnosis of the disease, since most of the time, the confirmation of motor problems and thus the confirmation that a patient is suffering from this disease, comes when the pathogenesis has progressed quite enough and a large part of the dopaminergic system has already suffered significant losses. Another reason that makes the study of this class of symptoms absolutely important is the fact that apart from the dopaminergic, other neurotransmission systems also seem to malfunction in Parkinson's disease.
Although motor symptoms have been extensively studied through the use of experimental animal models, non-motor symptoms show significant drawbacks in terms of recognition, research and also treatment. Τhus the purpose of this study is the evaluation of the early non-motor symptoms of Parkinson's disease in a new genetically modified animal model (rat model), which over-expresses the whole gene of human wild type α-synuclein, as well as the analysis of the neurochemical profile of these animals.
According to our results and through a behavioral point of view, we observed that these transgenic mice which overexpress α-synuclein in brain areas where the protein is normally expressed, exhibit from an early age of a great number of non-motor symptoms. More specifically, our transgenic animals exhibit a hyperactive phenotype which seems to be accompanied by a decreased anxiety behavior. The phenotype of anosmia, one of the first symptoms observed in patients suffering from the disease, became apparent in these rats even from 3 months of age. In later stages, neuropsychiatric symptoms such as depressive-like behaviors and cognitive deficits were also observed. Lastly, we also observed sensorimotor gating deficits. In regards to the neurochemical analysis, we observed that these rats exhibit dysfunction in specific neurotransmitter systems, such as the glutamatergic and the GABAergic system, which confirms the presence of these non-motor symptoms, as in general non-motor symptoms seem to represent the expression of the malfunction of these non-dopaminergic systems.
Keywords:
Parkinson, a-synuclein, Non motor symptoms, Rat
