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Assessing Neuroinflammation-related Neural Damage by Monitoring the Retinotectal System

PD Dr. Janos Groh - Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg
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Description

Neuroinflammation amplifies neural damage and disease outcome in models of various disorders. These disorders are often caused by gene defects, such as distinct leukodystrophies or lysosomal storage diseases. We recently could show that the normal aging process is also associated with chronic neuroinflammation. Similar to the genetic disease models, myelinated axons are especially vulnerable to aging-related degeneration.

To investigate the impact of secondary neuroinflammation after primary neural perturbation, we routinely take advantage of the retinotectal system in mice. The retinotectal system comprises well characterized and accessible compartments of the central nervous system (CNS), and allows both invasive and non-invasive monitoring of disease progression.

Using a combination of neurobiological and immunological techniques, we found that the accumulation of cytotoxic CD8+ T cells in the aged CNS leads to axon degeneration and contributes to behavioral decline. In addition to identifying mechanistic details, we observed that systemic inflammation aggrevates T cell-mediated damage in aged mice, but not in adult mice. CD8+ T cells might therefore represent a putative target for therapeutic approaches to mitigate structural and functional decline of the CNS related to disease or aging. Pre-clinical therapeutic approaches targeting inflammation support this hypothesis in the genetic disease models. This also confirms that monitoring the retinotectal system can be a valuable strategy to assess treatment efficacy.

Key Topics

  • Invasive and non-invasive readouts for assessment of retinotectal integrity.
  • Neuroinflammatory reactions in diseased or aged CNS white matter.
  • Animal experiments to characterize and analyze the impact of neuroinflammation.
  • Pre-clinical pharmacological therapy trials in disease models.

Learning Objectives

  • The properties of the retinotectal system make it an ideal surrogate to evaluate perturbation of specific CNS compartments.
  • Genetic defects in myelinating glial cells or aging-related perturbation result in chronic neuroinflammation of CNS white matter.
  • Secondary neuroinflammation can drive structural and functional decline of myelinated axons, contributing to behavioral deficits in mice.
  • Modulating neuroinflammation offers distinct therapeutic opportunities of high translational relevance.

Background Reading

Accumulation of cytotoxic T cells in the aged CNS leads to axon degeneration and contributes to cognitive and motor decline. Groh J, Knöpper K, Arampatzi P, Yuan X, Lößlein L, Saliba AE, Kastenmüller W, Martini R.
Nature Aging 1, 357–367 (2021).
doi: 10.1038/s43587-021-00049-z.

Immune modulation attenuates infantile
neuronal ceroid lipofuscinosis in mice before
and after disease onset.
Groh J, Berve K, Martini R.
Brain Communications 3(2), 1–12 (2021).
doi:10.1093/braincomms/fcab047.

Targeting microglia attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations. Groh J, Klein D, Berve K, West B L, Martini R.
GLIA 67(2), 277–290 (2019).
doi:10.1002/glia.23539.

Review:

The retina as a window to the brain – from eye research to CNS disorders. London A, Benhar I, Schwartz M.
Nat. Rev. Neurol. 9, 44–53 (2013).
doi:10.1038/nrneurol.2012.227.

About the speaker

PD Dr. Janos Groh

PD Dr. Janos Groh

Lecturer and Senior Research Associate
Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg

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PD Dr. Janos Groh was born in Germany and studied Biology with a focus on Neurobiology and Genetics at the University of Würzburg. He attained his PhD in the laboratory of Prof. Dr. Rudolf Martini at the Department of Neurology, University Hospital Würzburg. There he developed a strong interest in the complex interactions of the nervous system and the immune system and the contribution of neuroinflammation to various genetically mediated neurological diseases. He continued his work on these topics as a postdoctoral researcher and project leader and qualified as a lecturer in “Experimental Neurology”, broadening his research scope to include aging-related degenerative processes in the nervous system.

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Journal Club: Assessing Neuroinflammation-related Neural Damage by Monitoring the Retinotectal System
May 27th, 2021

    Striatech Journal Club - University Hospital Würzburg

    I already use optomotor measurementsI want to do optomotor measurements in the future

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