CNS distribution and overexpression of neurofilament light proteins (NF-L) in mice transgenic for the human NF-L: Aberrant accumulation in thalamic perikarya

Mathieu, Jean-François; Ma, Dongrui; Descarries, Laurent; Vallée, Annie; Parent, André; Julien, Jean‐Pierre; Doucet, Guy

doi:10.1016/0014-4886(95)90067-5

Cited by 13 publications

(16 citation statements)

References 28 publications

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“…NFL genotype analysis by PCR confirmed homozygous transgene or knock-out expression (data not shown). Consistent with previous descriptions (Ma et al, 1995;Mathieu et al, 1995;Zhu et al, 1997), white matter axons in the ventral fasciculus revealed a modest increase in axonal caliber and staining intensity in hNFL (1/1) mice and dramatic reductions in NFL (2/2) mice (data not shown). Neuropathologically, Bielschowsky silver stains confirmed the presence of aggregates in the perikarya of L4 ventral horn motor neurons (data not shown).…”

Section: Confirmation Of Nfl Expression Levelssupporting

confidence: 92%

Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(−/−)mice

McLean

Sanelli

Leystra-Lantz

et al. 2005

Glia

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Neurofilament (NF) aggregate formation within motor neurons is a pathological hallmark of both the sporadic and familial forms of amyotrophic lateral sclerosis (ALS). The relationship between aggregate formation and both microglial and astrocytic proliferation, as well as additional neuropathological features of ALS, is unknown. To examine this, we have used transgenic mice that develop NF aggregates, through either a lack of the low-molecular-weight NF subunit [NFL (-/-)] or the overexpression of human NFL [hNFL (+/+)]. Transgenic and wild-type C57bl/6 mice were examined from 1 month to 18 months of age, and the temporal pattern of motor neuron degeneration, microglial and astrocytic proliferation, and heat shock protein-70 (HSP-70) expression characterized. We observed three overlapping phases in both transgenic mice, including transient aggregate formation, reactive microgliosis, and progressive motor neuron loss. However, only NFL (-/-) mice demonstrated significant astrogliosis and HSP-70 upregulation in both motor neurons and astrocytes. These in vivo models suggest that the development of NF aggregates in motor neurons leads to motor neuron death, but that the interaction between the degenerating motor neurons and the adjacent non-neuronal cells may differ significantly depending on the etiology of the NF aggregate itself.

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Section: Confirmation Of Nfl Expression Levelssupporting

confidence: 92%

Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(−/−)mice

McLean

Sanelli

Leystra-Lantz

et al. 2005

Glia

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“…NF-L as a reliable regional marker-comparison with SMI-32 NF-L distribution in the mouse brain had been previously reported by Mathieu et al (1995) in a comparative study of normal mice and mice transgenic for human NF-L. This short report generally agrees with our more detailed analysis.…”

Section: Nf-l Content and Myelinationsupporting

confidence: 90%

“…However, the corpus callosum, internal capsule, and anterior commissure were reported by Mathieu et al (1995) to be immunonegative, whereas these major white matter tracts were intensely stained for NF-L in our study. In the cerebral cortex, Mathieu et al (1995) reported faint cell body staining that was visible in layers II, III, and V of the sensory cortices, comparable to what was observed in our study. Furthermore, these authors discerned NF-L-immunostained cells only in layers V and VI in the retrosplenial cortex.…”

Section: Nf-l Content and Myelinationcontrasting

confidence: 75%

“…These neurochemical studies have used the monoclonal antibody SMI-32 that recognizes the non-phosphorylated epitopes on NF-H and NF-M (Sternberger and Sternberger 1983), as a tool to detect regional and laminar variations in NFP expression patterns. The third subunit, NF-L, has not been investigated extensively as a neurochemical marker of topographic borders of cortical areas in mammals (Mathieu et al 1995).…”

Section: Introductionmentioning

confidence: 99%

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Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit

et al. 2011

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The expression patterns of the medium- and high-molecular-weight subunits of the neurofilament protein triplet have been extensively studied in several neuroanatomical studies. In the present study, we report the use of the low-molecular-weight neurofilament protein subunit (NF-L) as a reliable marker within the neurofilament protein family to reveal the regional architecture of mammalian neocortex. We document clearly its usefulness in anatomical parcellation studies and report unique expression patterns of NF-L throughout the mouse neocortex. NF-L was most abundant in the somatosensory cortex, the lateral secondary visual area, the granular insular cortex, and the motor cortex. Low NF-L staining intensity was observed in the agranular insular cortex, the prelimbic and infralimbic cortex, the anterior cingulate cortex, the visual rostromedial areas, the temporal association cortex, the ectorhinal cortex, and the lateral entorhinal cortex. NF-L immunoreactivity was present in the perikarya, dendrites, and proximal segment of axons primarily of pyramidal neurons, and was mainly located in layers II and III, and to a lesser extent in layers V and VI. Interestingly, Black-Gold myelin staining confirmed a close correlation between NF-L immunoreactivity and myelination patterns. The characteristic and distinctive distribution and laminar expression profiles of NF-L make it an excellent tool to assess accurately topographical boundaries among neocortical areas as illustrated herein in the adult mouse brain.

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“…NF-L is known to self-assemble into core filaments that then form cross-bridges with NF-M or NF-H (Fuchs and Weber, 1994;Nakagawa et al, 1995). Recent studies have revealed that overexpression or point mutation of NF-L can result in abnormal NF assembly and aggregation in neuronal cell bodies (Cote et al, 1993;Xu et al, 1993;Mathieu et al, 1995;Carter et al, 1996;Lee et al, 2008). NF aggregations due to overexpression or point mutations of NF-L have been associated with neurodegenerative diseases such as Charcot-Marie-Tooth disease (Watson et al, 1994;Fabrizi et al, 2004), Alzheimer's disease (Shepherd et al, 2002;Norgren et al, 2003) and amyotrophic lateral sclerosis (Hirano et al, 1984;Collard et al, 1995;Al-Chalabi and Miller, 2003).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol phosphates directly bind to neurofilament light chain (NF-L) for the regulation of NF-L self assembly

Kim

Yang

et al. 2011

Exp Mol Med

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Phosphatidylinositol phosphates (PtdInsPs) are ubiquitous membrane phospholipids that play diverse roles in cell growth and differentiation. To clarify the regulation mechanism acting on neurofilament light chain (NF-L) self assembly, we examined the effects of various PtdInsPs on this process. We found that PtdInsPs, including PI(4,5)P 2 , directly bind to the positively charged Arg 54 of murine NF-L, and this binding promotes NF-L self assembly in vitro. Mutant NF-L (R53A/R54A) proteins lacking binding affinity to PtdInsPs did not have the same effect, but the mutant NF-L proteins showed greater self assembly than the wild-type in the absence of any PtdInsP. These results collectively suggest that Arg 54 plays a pivotal role in NF-L self assembly by binding with PtdInsPs.

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CNS distribution and overexpression of neurofilament light proteins (NF-L) in mice transgenic for the human NF-L: Aberrant accumulation in thalamic perikarya

Cited by 13 publications

References 28 publications

Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(−/−)mice

Temporal profiles of neuronal degeneration, glial proliferation, and cell death in hNFL(+/+) and NFL(−/−)mice

Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit

Phosphatidylinositol phosphates directly bind to neurofilament light chain (NF-L) for the regulation of NF-L self assembly

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