Intra-familial phenotypic heterogeneity in adult onset vanishing white matter disease

Damon-Perrière, Nathalie; Ménégon, Patrice; Anne, Olivier; Boespflug‐Tanguy, Odile; Niel, Florence; Creveaux, Isabelle; Dousset, V.; Brochet, Bruno; Goizet, Cyril

doi:10.1016/j.clineuro.2008.08.003

Cited by 12 publications

(2 citation statements)

References 15 publications

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“…In human leukodystrophies, such as X-linked adreno-leukodystrophy and vanishing white matter disease, there have been anecdotal reports of head injuries causing disease or deteriorating its progression (Damon-Perriere et al, 2008;Espay et al, 2002;Raymond et al, 2010), and also the risk of multiple sclerosis may be increased following brain injury (Kang and Lin, 2012). In human leukodystrophies, such as X-linked adreno-leukodystrophy and vanishing white matter disease, there have been anecdotal reports of head injuries causing disease or deteriorating its progression (Damon-Perriere et al, 2008;Espay et al, 2002;Raymond et al, 2010), and also the risk of multiple sclerosis may be increased following brain injury (Kang and Lin, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The demonstration that minor neurotrauma modulates a genetic disease, and thus becomes an ''environmental'' risk factor, at least for the degree of myelin-associated neuropathology in Cnp1 mutant mice, has implications for other inflammatory white matter disorders. In human leukodystrophies, such as X-linked adreno-leukodystrophy and vanishing white matter disease, there have been anecdotal reports of head injuries causing disease or deteriorating its progression (Damon-Perriere et al, 2008;Espay et al, 2002;Raymond et al, 2010), and also the risk of multiple sclerosis may be increased following brain injury (Kang and Lin, 2012). Likewise, head trauma has been identified as an associated risk factor for psychiatric diseases, such as Alzheimer's disease and schizophrenia (Bryant et al, 2010;Molloy et al, 2011;Sastre et al, 2011;Van Den Heuvel et al, 2007;Whelan-Goodinson et al, 2009).…”

Section: ; Lappementioning

confidence: 99%

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Neuroinflammation in white matter tracts of Cnp1 mutant mice amplified by a minor brain injury

Wieser

Gerwig

Adamcio

et al. 2013

Glia

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Oligodendrocytes make myelin for rapid impulse propagation and contribute to the long-term survival of myelinated axons. The mechanisms by which oligodendroglial dysfunction(s) contribute to slowly progressive neurodegeneration are not well understood. Here, we demonstrate in Cnp1 mutant mice that secondary axonal degeneration in the subcortical white matter is associated with an age-dependent activation of both, innate and adaptive immune responses, including an expansion of infiltrating CD8+ T cells. While the detrimental role of lymphocytes in inherited myelin diseases is known, the role of activated microglia for the hypothetical cycle of inflammation/degeneration is unclear. We used a mild standardized cryolesion of the right parietal cortex to activate microglia at the vulnerable age of mouse puberty (postnatal day (P) 28). When applied to Cnp1 mutant mice, analyzed more than 3 months later, minor brain injury had acted as a "second hit" and significantly enhanced astrogliosis, microgliosis and axon degeneration, but not T cell infiltration. Interestingly, exacerbated neuropathological changes were also reflected by specific deterioration of working memory on top of an essentially normal basic behavior. We propose a model in which oligodendroglial dysfunctions can trigger a vicious cycle of neurodegeneration and low-grade inflammation that is amplified by nonspecific activators of the innate immune system. This interaction of genetic and environmental factors may be relevant for neuropsychiatric diseases associated with secondary neuroinflammation.

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