HYBRID EVENT: You can participate in person at Orlando, USA or Virtually from your home or work.

6th Edition of International Conference on Neurology and Brain Disorders

October 24 -26, 2022

October 24 -26, 2022 | Orlando, Florida, USA
INBC 2022

Judith Stefanie Scheller

Speaker at Neurology and Brain Disorders 2022 - Judith Stefanie Scheller
Institute of Physiological Chemistry, Ulm University, Germany
Title : NF-kB is a critical mediator of age-dependent white matter loss

Abstract:

Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic proinflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration is a well-described process in the aging brain which manifests in myelin loss finally resulting in neurological deficits. However, understanding of the underlying molecular mechanisms remains limited. Oligodendrocytes and their precursor cells are responsible for production, homeostasis and maintenance of the myelin sheaths. Mature oligodendrocytes are highly energy demanding cells due to their unique functions, and thus highly sensitive to different forms of stress. So far it is open how altered inflammatory conditions like inflammaging affect homeostasis and function of oligodendrocytes. We investigated the role of NF-kB, a well-known mediator of inflammatory and stress responses, in the homeostatic control of oligodendrocytes using a conditional gain-of-function mouse model allowing oligodendrocyte-specific activation of IKK/NF-kB signaling (IKK2-CAPLP-CreERT2) in the adult organism. Chronic NF-kB activation in mature oligodendrocytes was sufficient to initiate overall neuroinflammatory conditions in the CNS accompanied by motoric and neurological deficits which progress with age. Ultrastructural analyses revealed degeneration of the corpus callosum as well as loss of myelin sheaths and accordingly, myelin proteins were found decreased in IKK2-CAPLP-CreERT2 mice. Interestingly, RNA-Seq analysis of isolated primary oligodendrocytes revealed gene expression signatures pointing to NF-kB mediated integrated stress response (IRS), senescence associated secretory phenotype (SASP) and post mitotic cellular senescence (PoMiCS) appearing prior to white matter loss. Taken together, our data indicate that IKK/NF-kB signaling, a central effector of diverse stress responses, is able to trigger PoMiCS of mature oligodendrocytes thereby disturbing myelin maintenance and finally forcing aging-dependent white matter loss. What will audience learn from your presentation? • Selective NF-kB activation in mature oligodendrocytes is able to initiate global neuroinflammation in the brain • Post-mitotic cellular senescence of mature oligodendrocytes is critically regulated by NF-kB/inflammaging • Integrated stress responses and cellular senescence are important mediators of white matter loss • Cell-type-specific interference with NF-κB function or downstream effectors offer new therapeutic strategies to attenuate age-dependent white matter degeneration

Biography:

Judith Stefanie Scheller graduated with a degree in Food Chemistry and Toxicology in 2016 from the Karlsruhe Institute of Technology. Afterwards she worked 2 years on protein misfolding and amyloidosis before she joined the group of Prof. Dr. Thomas Wirth to obtain her PhD within the excellence programme of the International Graduate School of Molecular Medicine at Ulm University. She is about to finish her PhD working on inflammation driven neurodegeneration

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