Groh, Janos and Kuehl, Thomas G. and Ip, Chi Wang and Nelvagal, Hemanth R. and Sri, Sarmi and Duckett, Steven and Mirza, Myriam and Langmann, Thomas and Cooper, Jonathan D. and Martini, Rudolf (2013) Immune cells perturb axons and impair neuronal survival in a mouse model of infantile neuronal ceroid lipofuscinosis. BRAIN, 136. pp. 1083-1101. ISSN 0006-8950, 1460-2156
Full text not available from this repository. (Request a copy)Abstract
The neuronal ceroid lipofuscinoses are fatal neurodegenerative disorders in which the visual system is affected early in disease progression. A typical accompanying feature is neuroinflammation, the pathogenic impact of which is presently obscure. Here we investigated the role of inflammatory cells in palmitoyl protein thioesterase 1-deficient (Ppt1(-/-)) mice, a model of infantile neuronal ceroid lipofuscinosis (CLN1 disease, infantile), predominantly focusing on the visual system. We detected an early infiltration of CD8+ T-lymphocytes and observed activation of microglia/macrophage-like cells. To analyse the pathogenic impact of lymphocytes, we crossbred Ppt1(-/-) mice with mutants lacking lymphocytes (Rag1(-/-)), and scored axonal transport, axonal perturbation and neuronal survival. This lack of lymphocytes led to a significant amelioration of disease phenotypes, not only in the retino-tectal system, but also in other regions of the central nervous system. Finally, reconstitution experiments revealed a crucial role of CD8+ T-lymphocytes in pathogenesis. Our study provides novel pathomechanistic insights that may be crucial for developing treatment strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BLOOD-BRAIN-BARRIER; BATTEN-DISEASE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; NEURAL DAMAGE; MUTANT MICE; OPTIC-NERVE; PROTEIN; DEGENERATION; CNS; neuronal ceroid lipofuscinosis; neurodegeneration; neuroinflammation; T-lymphocytes; axonal damage |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2020 05:03 |
| Last Modified: | 20 Apr 2020 05:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16909 |
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