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BMC Neurology
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Amyotrophic lateral sclerosis modifies progenitor neural proliferation in adult classic neurogenic brain niches

Authors: Lucía Galán, Ulises Gómez-Pinedo, Antonio Guerrero, Jose Manuel García-Verdugo, Jorge Matías-Guiu

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

Adult neurogenesis persists through life at least in classic neurogenic niches. Neurogenesis has been previously described as reduced in neurodegenerative diseases. There is not much knowledge about is adult neurogenesis is or not modified in amyotrophy lateral sclerosis (ALS). All previous publications has studied the ALS SOD1 (superoxide dismutase) transgenic mouse model. The purpose of this study is to examine the process of adult neurogenesis in classic niches (subventricular zone [SVZ] and subgranular zone [SGZ] of the dentate gyrus) in patients with amyotrophic lateral sclerosis (ALS), both with (ALS-FTD) and without associated frontotemporal dementia (FTD).

Methods

We studied 9 autopsies of patients with ALS (including 2 with ALS-FTD) and 4 controls. ALS was confirmed histologically. Studies of the SVZ and SGZ were conducted using markers of proliferation (Ki-67, PCNA), of pluripotent neural progenitor cells (GFAPδ), neuroblasts (PSA-NCAM, DCX, TUJ1), and an astrocyte marker (GFAP). Results were analyzed with non-parametric tests. We then studied correlations between the different markers and the percentage of phosphorylated TDP-43 (pTDP-43).

Results

We observed a statistically significant increase in proliferation in the SVZ in all patients with ALS. While this increase was more marked in ALS forms associated with dementia, the small sample size does not permit a statistical subgroup analysis. In contrast, proliferation in the SGZ was decreased in all patients. These alterations showed a positive and direct correlation with the percentage of pTDP-43 in the SVZ, and a negative, exponential correlation with that percentage in the SGZ.

Conclusions

We observed alterations of the proliferation of neural progenitor in classic adult neurogenic niches in patients with ALS. The 2 neurogenic niches exhibited opposite changes such that proliferation increased in the SVZ and decreased in the SGZ.
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Literature
1.
2.
Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–7.CrossRefPubMed
3.
Seri B, Garcia-Verdugo JM, Collado-Morente L, McEwen BS, Alvarez-Buylla A. Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol. 2004;478:359–78.CrossRefPubMed
4.
Quinones-Hinojosa A, Sanai N, Gonzalez-Perez O, Garcia-Verdugo JM. The human brain subventricular zone: stem cells in this niche and its organization. Neurosurg Clin N Am. 2007;18:15–20. viiCrossRefPubMed
5.
Oyarce K, Bongarzone ER, Nualart F. Unconventional Neurogenic niches and neurogenesis modulation by vitamins. J Stem Cell Res Ther. 2014;4:184.PubMedPubMedCentral
6.
7.
Kempermann G. Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci. 2002;22:635–8.PubMed
8.
Lazarini F, Lledo PM. Is adult neurogenesis essential for olfaction? Trends Neurosci. 2011;34:20–30.CrossRefPubMed
9.
Marti-Fabregas J, Romaguera-Ros M, Gomez-Pinedo U, et al. Proliferation in the human ipsilateral subventricular zone after ischemic stroke. Neurology. 2010;74:357–65.CrossRefPubMed
10.
11.
Beeldman E, Raaphorst J, Klein Twennaar M, de Visser M, Schmand BA, de Haan RJ. The cognitive profile of ALS: a systematic review and meta-analysis update. J Neurol Neurosurg Psychiatry. 2016;87(6):611–9. doi:10.​1136/​jnnp-2015-310734.
12.
Matias-Guiu JA, Pytel V, Cabrera-Martin MN, et al. Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis. Eur J Nucl Med Mol Imaging. 2016;43:2050–60.CrossRefPubMed
13.
14.
Cykowski MD, Powell SZ, Peterson LE, et al. Clinical significance of TDP-43 neuropathology in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 2017;76:402–13.CrossRefPubMed
15.
Brettschneider J, Del Tredici K, Irwin DJ, et al. Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol. 2014;127:423–39.CrossRefPubMedPubMedCentral
16.
Ng AS, Rademakers R, Miller BL. Frontotemporal dementia: a bridge between dementia and neuromuscular disease. Ann N Y Acad Sci. 2015;1338:71–93.CrossRefPubMed
17.
Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2007;24(1):CD001447.
18.
Chi L, Gan L, Luo C, Lien L, Liu R. Temporal response of neural progenitor cells to disease onset and progression in amyotrophic lateral sclerosis-like transgenic mice. Stem Cells Dev. 2007;16:579–88.CrossRefPubMed
19.
Chi L, Ke Y, Luo C, et al. Motor neuron degeneration promotes neural progenitor cell proliferation, migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice. Stem Cells. 2006;24:34–43.CrossRefPubMed
20.
Warita H, Murakami T, Manabe Y, et al. Induction of polysialic acid-neural cell adhesion molecule in surviving motoneurons of transgenic amyotrophic lateral sclerosis mice. Neurosci Lett. 2001;300:75–8.CrossRefPubMed
21.
Galan L, Gomez-Pinedo U, Vela-Souto A, et al. Subventricular zone in motor neuron disease with frontotemporal dementia. Neurosci Lett. 2011;499:9–13.CrossRefPubMed
22.
Kee N, Sivalingam S, Boonstra R, Wojtowicz JM. The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J Neurosci Methods. 2002;115:97–105.CrossRefPubMed
23.
Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol. 2006;494:415–34.CrossRefPubMed
24.
Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17:5046–61.PubMed
25.
Garcia AD, Doan NB, Imura T, Bush TG, Sofroniew MV. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci. 2004;7:1233–41.CrossRefPubMed
26.
Gomez-Pinedo U, Galan L, Yanez M, et al. Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease. Neurologia. 2016;25(16)30167–0. doi:10.​1016/​j.​nrl.​2016.​07.​002.
27.
Kamphuis W, Mamber C, Moeton M, et al. GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS One. 2012;7:e42823.CrossRefPubMedPubMedCentral
28.
Seki T. Expression patterns of immature neuronal markers PSA-NCAM, CRMP-4 and NeuroD in the hippocampus of young adult and aged rodents. J Neurosci Res. 2002;70:327–34.CrossRefPubMed
29.
Dennis CV, Suh LS, Rodriguez ML, Kril JJ, Sutherland GT. Human adult neurogenesis across the ages: an immunohistochemical study. Neuropathol Appl Neurobiol. 2016;42:621–38.CrossRefPubMed
30.
Francis F, Koulakoff A, Boucher D, et al. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron. 1999;23:247–56.CrossRefPubMed
31.
von Bohlen Und Halbach O. Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res. 2007;329:409–20.CrossRef
32.
Baralle M, Buratti E, Baralle FE. The role of TDP-43 in the pathogenesis of ALS and FTLD. Biochem Soc Trans. 2013;41:1536–40.CrossRefPubMed
33.
34.
35.
Thompson A, Boekhoorn K, Van Dam AM, Lucassen PJ. Changes in adult neurogenesis in neurodegenerative diseases: cause or consequence? Genes Brain Behav. 2008;7(Suppl 1):28–42.CrossRefPubMed
36.
Curtis MA, Penney EB, Pearson AG, et al. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci U S A. 2003;100:9023–7.CrossRefPubMedPubMedCentral
37.
38.
Boekhoorn K, Joels M, Lucassen PJ. Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis. 2006;24:1–14.CrossRefPubMed
39.
Mirochnic S, Wolf S, Staufenbiel M, Kempermann G. Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease. Hippocampus. 2009;19:1008–18.CrossRefPubMed
40.
Bossers K, Wirz KT, Meerhoff GF, et al. Concerted changes in transcripts in the prefrontal cortex precede neuropathology in Alzheimer's disease. Brain. 2010;133:3699–723.CrossRefPubMed
41.
Kohl Z, Kandasamy M, Winner B, et al. Physical activity fails to rescue hippocampal neurogenesis deficits in the R6/2 mouse model of Huntington's disease. Brain Res. 2007;1155:24–33.CrossRefPubMed
42.
Simpson JM, Gil-Mohapel J, Pouladi MA, et al. Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease. Neurobiol Dis. 2011;41:249–60.CrossRefPubMed
43.
Curtis MA, Penney EB, Pearson J, Dragunow M, Connor B, Faull RL. The distribution of progenitor cells in the subependymal layer of the lateral ventricle in the normal and Huntington's disease human brain. Neuroscience. 2005;132:777–88.CrossRefPubMed
44.
Guan YJ, Wang X, Wang HY, et al. Increased stem cell proliferation in the spinal cord of adult amyotrophic lateral sclerosis transgenic mice. J Neurochem. 2007;102:1125–38.CrossRefPubMed
45.
46.
Gil-Perotin S, Alvarez-Buylla A, Garcia-Verdugo JM. Identification and characterization of neural progenitor cells in the adult mammalian brain. Adv Anat Embryol Cell Biol. 2009;203:1–101. ixCrossRefPubMed
47.
Barkho BZ, Zhao X. Adult neural stem cells: response to stroke injury and potential for therapeutic applications. Curr Stem Cell Res Ther. 2011;6:327–38.CrossRefPubMedPubMedCentral
48.
49.
Yanez M, Matias-Guiu J, Arranz-Tagarro JA, et al. The neuroprotection exerted by memantine, minocycline and lithium, against neurotoxicity of CSF from patients with amyotrophic lateral sclerosis, is antagonized by riluzole. Neurodegener Dis. 2014;13:171–9.CrossRefPubMed
50.
Yanez M, Galan L, Matias-Guiu J, Vela A, Guerrero A, Garcia AG. CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: protection by resveratrol but not riluzole. Brain Res. 2011;1423:77–86.CrossRefPubMed
51.
Batiz LF, Castro MA, Burgos PV, et al. Exosomes as novel regulators of adult neurogenic niches. Front Cell Neurosci. 2015;9:501.PubMed
52.
Paredes MF, Sorrells SF, Garcia-Verdugo JM, Alvarez-Buylla A. Brain size and limits to adult neurogenesis. J Comp Neurol. 2016;524:646–64.CrossRefPubMed
Metadata
Title
Amyotrophic lateral sclerosis modifies progenitor neural proliferation in adult classic neurogenic brain niches
Authors
Lucía Galán
Ulises Gómez-Pinedo
Antonio Guerrero
Jose Manuel García-Verdugo
Jorge Matías-Guiu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0956-5

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