PMID- 22046428
OWN - NLM
STAT- MEDLINE
DCOM- 20120326
LR  - 20240214
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 10
DP  - 2011
TI  - Genetic ablation of PLA2G6 in mice leads to cerebellar atrophy characterized by 
      Purkinje cell loss and glial cell activation.
PG  - e26991
LID - 10.1371/journal.pone.0026991 [doi]
LID - e26991
AB  - Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive 
      neurodegenerative disease characterized by axonal dystrophy, abnormal iron 
      deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, 
      which encodes group VI Ca(2+)-independent phospholipase A(2) (iPLA(2) or 
      iPLA(2)beta). Here we show that genetic ablation of PLA2G6 in mice (iPLA(2)beta(-/-)) 
      leads to the development of cerebellar atrophy by the age of 13 months. Atrophied 
      cerebella exhibited significant loss of Purkinje cells, as well as reactive 
      astrogliosis, the activation of microglial cells, and the pronounced 
      up-regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) 
      and interleukin-1beta (IL-1beta). Moreover, glial cell activation and the elevation in 
      TNF-alpha and IL-1beta expression occurred before apparent cerebellar atrophy. Our 
      findings indicate that the absence of PLA2G6 causes neuroinflammation and 
      Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests 
      that iPLA(2)beta(-/-) mice are a valuable model for cerebellar atrophy in INAD and 
      that early anti-inflammatory therapy may help slow the progression of cerebellar 
      atrophy in this deadly neurodegenerative disease.
FAU - Zhao, Zhengshan
AU  - Zhao Z
AD  - Division of Experimental Diabetes and Aging, Department of Geriatrics and 
      Palliative Medicine, Mount Sinai School of Medicine, New York, New York, United 
      States of America.
FAU - Wang, Jing
AU  - Wang J
FAU - Zhao, Chunying
AU  - Zhao C
FAU - Bi, Weina
AU  - Bi W
FAU - Yue, Zhenyu
AU  - Yue Z
FAU - Ma, Zhongmin Alex
AU  - Ma ZA
LA  - eng
GR  - R01 NS060809/NS/NINDS NIH HHS/United States
GR  - R01 NS063962/NS/NINDS NIH HHS/United States
GR  - R01NS060809/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111028
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (Pla2g6 protein, mouse)
SB  - IM
MH  - Animals
MH  - Atrophy/*genetics
MH  - Cerebellar Diseases/genetics/*pathology
MH  - Group VI Phospholipases A2/*deficiency/genetics
MH  - Interleukin-1beta
MH  - Mice
MH  - Microglia
MH  - Neuroaxonal Dystrophies
MH  - Neuroglia/immunology/*pathology
MH  - Purkinje Cells/*pathology
MH  - Tumor Necrosis Factor-alpha
PMC - PMC3203935
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/11/03 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/10/28
CRDT- 2011/11/03 06:00
PHST- 2011/07/22 00:00 [received]
PHST- 2011/10/07 00:00 [accepted]
PHST- 2011/11/03 06:00 [entrez]
PHST- 2011/11/03 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/10/28 00:00 [pmc-release]
AID - PONE-D-11-14083 [pii]
AID - 10.1371/journal.pone.0026991 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(10):e26991. doi: 10.1371/journal.pone.0026991. Epub 2011 Oct 28.