Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms

Hol, Elly M.; Roelofs, Reinko F.; Moraal, Ewoud; Sonnemans, M. A. F.; Sluijs, Jacqueline A.; Proper, E.A.; Graan, P.N.E. de; Fischer, David F.; Leeuwen, Fred W. van

doi:10.1038/sj.mp.4001379

Cited by 138 publications

(131 citation statements)

References 44 publications

(58 reference statements)

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…3), we demonstrated that GFAPd is expressed in a subpopulation of all GFAP-expressing cells in the developing human brain. More differentiated or matured astrocytes in other areas of the developing brain lacked GFAPd expression, but might express other isoforms of GFAP (Blechingberg et al, 2007;Hol et al, 2003). These results are in accordance with the study by Pollard et al showing that GFAPd levels decrease following in vitro differentiation (Pollard et al, 2009).…”

Section: Discussionsupporting

confidence: 82%

“…We combined GFAPd with monoclonal mouse antibodies against vimentin (clone V9; DAKO; 1:1000), a known marker of radial glia in the VZ during human brain development (Honig et al, 1996), nestin (MAB5326, Chemicon; 1:200), a marker of both a subpopulation of radial glia (Zecevic, 2004) and SVZ neural progenitors (Lendahl et al, 1990), Ki67 (clone MIB-1, DAKO; 1:200), a marker of proliferation (Scholzen and Gerdes, 2000), and with polyclonal rabbit antibody against Sox2 (AB5603, Chemicon; 1:200), a transcription factor important for the maintenance of neural stem cells (Graham et al, 2003). For double labelling with polyclonal goat antibody against the C terminus of GFAP, which could, in principle, also detect other low-expressed GFAP isoforms, for example, GFAP135 (Hol et al, 2003) (GFAP C-term; Santa Cruz Biotechnology; 1:200), we blocked with normal swine serum instead of normal goat serum. After incubation overnight with the primary antibodies at 4°C, sections were incubated for two hours at room temperature with Alexa Fluor 568-conjugated anti-rabbit IgG and Alexa Fluor ® 488 anti-mouse or anti-goat IgG (1:100, Molecular Probes, The Netherlands).…”

Section: Immunocytochemical Analysismentioning

confidence: 99%

See 1 more Smart Citation

GFAPδ in radial glia and subventricular zone progenitors in the developing human cortex

et al. 2010

View full text Add to dashboard Cite

SUMMARYA subpopulation of glial fibrillary acidic protein (GFAP)-expressing cells located along the length of the lateral ventricles in the subventricular zone (SVZ) have been identified as the multipotent neural stem cells of the adult mammalian brain. We have previously found that, in the adult human brain, a splice variant of GFAP, termed GFAPd, was expressed specifically in these cells. To investigate whether GFAPd is also present in the precursors of SVZ astrocytes during development and whether GFAPd could play a role in the developmental process, we analyzed GFAPd expression in the normal developing human cortex and in the cortex of foetuses with the migration disorder lissencephaly type II. We demonstrated for the first time that GFAPd is specifically expressed in radial glia and SVZ neural progenitors during human brain development. Expression of GFAPd in radial glia starts at around 13 weeks of pregnancy and disappears before birth. GFAPd is continuously expressed in the SVZ progenitors at later gestational ages and in the postnatal brain. Co-localization with Ki67 proved that these GFAPd-expressing cells are able to proliferate. Furthermore, we showed that the expression pattern of GFAPd was disturbed in lissencephaly type II. Overall, these results suggest that the adult SVZ is indeed a remnant of the foetal SVZ, which develops from radial glia. Furthermore, we provide evidence that GFAPd can distinguish resting astrocytes from proliferating SVZ progenitors.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Immunocytochemical Analysismentioning

confidence: 99%

GFAPδ in radial glia and subventricular zone progenitors in the developing human cortex

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Furthermore, in aged cynomolgus macaques, GFAP immunoreactive processes are present around Aβ and apoE plaques (Nakamura et al 1996). Interestingly, high expression levels of GFAP have also been associated with AD (Nichols et al 1993;Hol et al 2003;Si et al 2004), with higher GFAP expression found in subjects with apoE ε4 allele (Overmyer et al 1999).…”

mentioning

confidence: 99%

Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Haley

Kohama

Urbanski

et al. 2010

AGE

View full text Add to dashboard Cite

Loss of synaptic integrity in the hippocampus and prefrontal cortex (PFC) may play an integral role in age-related cognitive decline. Previously, we showed age-related increases in the dendritic marker microtubule associated protein 2 (MAP-2) and the synaptic marker synaptophysin (SYN) in mice. Similarly, apolipoprotein E (apoE), involved in lipid transport and metabolism, and glial fibrillary acidic protein (GFAP), a glia specific marker, increase with age in rodents. In this study, we assessed whether these four proteins show similar age-related changes in a nonhuman primate, the rhesus macaque. Freefloating sections from the PFC and hippocampus from adult, middle-aged, and aged rhesus macaques were immunohistochemically labeled for MAP-2, SYN, apoE, and GFAP. Protein levels were measured as area occupied by fluorescence using confocal microscopy as well as by Western blot. In the PFC and hippocampus of adult and middle-aged animals, the levels of SYN, apoE, and GFAP immunoreactivity were comparable but there was a trend towards higher MAP-2 levels in middle-aged than adult animals. There was significantly less SYN and more MAP-2, apoE, and GFAP immunoreactivity in the PFC and hippocampus of aged animals compared to adult or middle-aged animals. Thus, the age-related changes in MAP-2, apoE, and GFAP levels were similar to those previously observed in rodents. On the other hand, the age-related changes in SYN levels were not, but were similar to those previously observed in the aging human brain. Taken together, these data emphasize the value of the rhesus macaque as a pragmatic translational model for human brain aging.

show abstract

“…In contrast, the members of the IF protein family, which is encoded by 70 genes, have very different primary amino acid sequences but a common domain organization (4). In addition, an increasing number of alternative splice forms of individual IF proteins have been discovered recently (5). IF proteins are differentially expressed during embryonic development, in parallel to distinct routes of differentiation, indicating that they have distinct tissue-specific functions (6,7).…”

Section: Introductionmentioning

confidence: 99%

Intermediate filaments: primary determinants of cell architecture and plasticity

Herrmann

Strelkov²,

Burkhard³

et al. 2009

J. Clin. Invest.

279

288

View full text Add to dashboard Cite

Intermediate filaments (IFs) are major constituents of the cytoskeleton and nuclear boundary in animal cells. They are of prime importance for the functional organization of structural elements. Depending on the cell type, morphologically similar but biochemically distinct proteins form highly viscoelastic filament networks with multiple nanomechanical functions. Besides their primary role in cell plasticity and their established function as cellular stress absorbers, recently discovered gene defects have elucidated that structural alterations of IFs can affect their involvement both in signaling and in controlling gene regulatory networks. Here, we highlight the basic structural and functional properties of IFs and derive a concept of how mutations may affect cellular architecture and thereby tissue construction and physiology.

show abstract

Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms

Cited by 138 publications

References 44 publications

GFAPδ in radial glia and subventricular zone progenitors in the developing human cortex

GFAPδ in radial glia and subventricular zone progenitors in the developing human cortex

Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Intermediate filaments: primary determinants of cell architecture and plasticity

Contact Info

Product

Resources

About