Electroencefalografische karakterisatie van comorbiditeiten in neurodegeneratieve ziekten: van epilepsie tot insomnia
18 december 2019
UAntwerpen, Campus Drie Eiken, Gebouw S, Auditorium S1 - Universiteitsplein 1 - 2610 Wilrijk (Antwerpen) (route: UAntwerpen, Campus Drie Eiken
14 - 16 uur
Jan Van Erum
Peter Paul De Deyn, Debby Van Dam
Doctoraatsverdediging Jan Van Erum - Departement Biomedische Wetenschappen
Neurodegenerative diseases are often associated with comorbidities that worsen the disease phenotype. As our society might benefit from more effective therapeutic strategies for these comorbidities, we sought to provide a better characterization of the underlying mechanisms that play a role in their development. In this doctoral thesis, we focused on two comorbidities in particular, namely epilepsy and sleep disturbances.
Epilepsy is more prevalent in certain neurodegenerative diseases. Patients are more prone to the development of seizures and epilepsy than aged control individuals. As many of these neurodegenerative disorders are characterized by the presence of pathologic forms of tau and neurofibrillary tangles, studying the effects of tau pathology on the development of epilepsy might prove rewarding. To gain more insight into the relation between tau pathology and epileptogenesis, the Tau58/4 tauopathy mouse model was subjected to a seizure susceptibility analysis. We reported increased seizure susceptibility in young Tau58/4 mice, which are still in an early pathologic stage, but not in old Tau58/4 mice with full-blown tau pathology. Therefore, we hypothesized a crucial role for pre-fibrillar hyperphosphorylated tau in increasing the sensitivity towards PTZ-induced seizures.
Aside from epilepsy, many patients also suffer from other comorbidities, including sleep and circadian rhythm disturbances. In contrast to epilepsy, sleep abnormalities are among the first noticeable symptoms of the disease. To gain a better understanding of how certain dementia-specific pathologic proteins interact with sleep-regulating brain centers and influence cognition, two different transgenic mouse models were studied. We found that, at advanced stages of pathology, both models display severe sleep deficits. In APP23 mice, the sleep and activity profile hints towards a hyperactive condition during the dark phase. In Tau58/4 mice sleep time was reduced during both photoperiods. Most remarkably, disturbances in rapid eye movement sleep were already present from a young age. Based on the pathologic spread in the APP23 model and the spectral data of the EEG, we concluded that Aβ probably has toxic effects at the level of the cortex, resulting in disrupted patterns of cortical activation and sleep loss. By contrast, tau pathology might be more detrimental for the central regulation of sleep, regulated by sleep centers in the brainstem, because sleep disturbances are photoperiod-independent and arise around the time pathologic tau starts to accumulate in pontine regions. To conclude, Aβ and tau obviously have differential effects on sleep in these two distinct models.