Poster (download)
206
Mikhail Tyumentsev1, Natalia Muraleva2, Yulia Polienko3, Artyom Gorodetsky4, Elena Bagryanskaya5
1ICG SB RAS, landselur@bionet.nsc.ru
2ICG SB RAS, Myraleva@bionet.nsc.ru
3NIOCH SB RAS, polienko@nioch.nsc.ru
4NIOCH SB RAS, gorodaa@nioch.nsc.ru
5NIOCH SB RAS, egbagryanskaya@nioch.nsc.ru
This study focuses on the relationship between mitochondrial dysfunction and redox-status in the context of the development of signs of Alzheimer’s disease (AD). Mitochondrial dysfunction is considered the missing link between brain aging and AD [1], the most common type of age-related dementia worldwide, but the exact causal relationship between mitochondrial dysfunction and the transition from healthy aging to AD remains to be fully understood. Oxidative stress is thought to play a significant role in this mitochondrial dysfunction, leading to cellular damage in redox imbalance. However, the extent of these processes and timing of their occurrence within the scope of AD remain hard to study, especially so in the early, pre-clinical stages of the disease. We explored the mechanisms underlying the disruption of mitochondrial function, their impact on the initiation and progression of pathological molecular cascades of AD, and assessed the changes in redox status as one of the main consequences of oxidative stress. This investigation was conducted using senescence-accelerated OXYS rats, which spontaneously develop all major signs of AD and largely reproduce the stages of the disease. We concluded that mitochondrial dysfunction appears to mediate or possibly even initiate AD-like pathology in OXYS rats. Importantly this takes place with no apparent connection to redox imbalance as on both transcriptional and biochemical levels OXYS rats display no significant changes in redox-status and ROS production as compared to controls.
Thank you for the interesting, well done presentation.
You showed a decrease in mitochondrial quantity and function in the development of AD-like pathology in OXYS rats. It is known that in neurons of AD mice there are a broader variety of mitochondrial shapes ranging from ovoid, to teardrop profiles with tubular membrane extension at one or both ends and to teardrop shaped mitochondria connected by thin double membrane extending up to 5 μm long that was termed “mitochondria-on-a-string” (MOAS).
What do you think, the formation of MOAS is a pathological or compensatory process? Have you observed mitophagy?
Thank you for your question.
As with many processess found in living organisms, formation of MOAS might start as a compensatory reaction but has a potential to turn into pathology if MOAS become too persistent and begin interfering with axonal traffic. We have shown (Tyumentsev et al. – 2018, Biochemistry (Moscow)) that OXYS rats are characterized by increased formation of MOAS at the preclinical stage of the AD signs.
Regarding mitophagy, data on depletion of mitochondrial numbers and decreased fusion presented here might suggest that mitophagic activity is changed in OXYS rats comparing to controls. Previously in our lab we have shown (Kozhevnikova et al. – 2018, Biogerontology) that OXYS rats display signs of disruption of autophagy pathway which also regulates mitophagy.
This suggests that disruption of mitophagy plays a role in the development of neurodegeneration in OXYS rats.
Thank you for your clear reply
jazz instrumental
seaside cafe ambience
harp
relax music
relaxing jazz piano music
relaxing jazz instrumental music