PMID- 15920739
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20061115
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 52
IP  - 1
DP  - 2005 Oct
TI  - Temporal profiles of neuronal degeneration, glial proliferation, and cell death 
      in hNFL(+/+) and NFL(-/-) mice.
PG  - 59-69
AB  - 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.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - McLean, Jesse R
AU  - McLean JR
AD  - Department of Pathology, Schulich School of Medicine, University of Western 
      Ontario, London, Ontario, Canada.
FAU - Sanelli, Teresa R
AU  - Sanelli TR
FAU - Leystra-Lantz, Cheryl
AU  - Leystra-Lantz C
FAU - He, Bei Ping
AU  - He BP
FAU - Strong, Michael J
AU  - Strong MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (neurofilament protein L)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/genetics/metabolism/*physiopathology
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Death/physiology
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Gliosis/genetics/metabolism/*physiopathology
MH  - HSP70 Heat-Shock Proteins/genetics/metabolism
MH  - Inclusion Bodies/genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microglia/metabolism/pathology
MH  - Motor Neurons/metabolism/pathology
MH  - Nerve Degeneration/genetics/metabolism/*physiopathology
MH  - Neurofilament Proteins/*genetics
MH  - Time Factors
EDAT- 2005/05/28 09:00
MHDA- 2006/08/10 09:00
CRDT- 2005/05/28 09:00
PHST- 2005/05/28 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2005/05/28 09:00 [entrez]
AID - 10.1002/glia.20218 [doi]
PST - ppublish
SO  - Glia. 2005 Oct;52(1):59-69. doi: 10.1002/glia.20218.