PMID- 20382699
OWN - NLM
STAT- MEDLINE
DCOM- 20101004
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 176
IP  - 6
DP  - 2010 Jun
TI  - HIV and SIV induce alterations in CNS CaMKII expression and activation: a 
      potential mechanism for cognitive impairment.
PG  - 2776-84
LID - 10.2353/ajpath.2010.090809 [doi]
AB  - The molecular mechanisms underlying learning and memory impairment in patients 
      with HIV-associated neurological disease have remained unclear. 
      Calcium/calmodulin-dependent kinase II (CaMKII) has key roles in synaptic 
      potentiation and memory storage in neurons and also may have immunomodulatory 
      functions. To determine whether HIV and simian immunodeficiency virus (SIV) 
      induce alterations in CaMKII expression and/or activation (autophosphorylation) 
      in the brain, we measured CaMKII alterations by quantitative immunoblotting in 
      both an in vitro HIV/neuronal culture model and in vivo in an SIV-infected 
      macaque model of HIV-associated neurological damage. Using primary rat 
      hippocampal neuronal cultures treated with culture supernatants harvested from 
      HIV-1-infected human monocyte-derived macrophages (HIV/MDM), we found that CaMKII 
      activation declined after exposure of neurons to HIV/MDM. Consistent with our in 
      vitro measurements, a significant decrease in CaMKII activation was present in 
      both the hippocampus and frontal cortex of SIV-infected macaques compared with 
      uninfected animals. In SIV-infected animals, total CaMKII expression in the 
      hippocampus correlated well with levels of synaptophysin. Furthermore, CaMKII 
      expression in both the hippocampus and frontal cortex was inversely correlated 
      with viral load in the brain. These findings suggest that alterations in CaMKII 
      may compromise synaptic function in the early phases of chronic neurodegenerative 
      processes induced by HIV.
FAU - Gupta, Ravi G
AU  - Gupta RG
AD  - Department of Molecular and Comparative Pathobiology, Johns Hopkins University 
      School of Medicine, Baltimore, MD 21205-2196, USA.
FAU - Kelly, Kathleen M
AU  - Kelly KM
FAU - Helke, Kris L
AU  - Helke KL
FAU - Queen, Suzanne E
AU  - Queen SE
FAU - Karper, Jami M
AU  - Karper JM
FAU - Dorsey, Jamie L
AU  - Dorsey JL
FAU - Brice, Angela K
AU  - Brice AK
FAU - Adams, Robert J
AU  - Adams RJ
FAU - Tarwater, Patrick M
AU  - Tarwater PM
FAU - Kolson, Dennis L
AU  - Kolson DL
FAU - Mankowski, Joseph L
AU  - Mankowski JL
LA  - eng
GR  - R01 HL078479/HL/NHLBI NIH HHS/United States
GR  - T32 RR007002/RR/NCRR NIH HHS/United States
GR  - RR007002/RR/NCRR NIH HHS/United States
GR  - HL078479/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100409
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Synaptophysin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Frontal Lobe/cytology/*enzymology/pathology/*virology
MH  - HIV/*metabolism
MH  - HIV Infections/metabolism
MH  - Hippocampus/cytology/*enzymology/pathology/*virology
MH  - Humans
MH  - Macaca mulatta/metabolism/virology
MH  - Neurons/metabolism/virology
MH  - Rats
MH  - Simian Acquired Immunodeficiency Syndrome/metabolism
MH  - Simian Immunodeficiency Virus/*metabolism
MH  - Synapses/metabolism
MH  - Synaptophysin/metabolism
MH  - Viral Load
PMC - PMC2877839
EDAT- 2010/04/13 06:00
MHDA- 2010/10/05 06:00
PMCR- 2011/06/01
CRDT- 2010/04/13 06:00
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - S0002-9440(10)60799-7 [pii]
AID - 10.2353/ajpath.2010.090809 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 Jun;176(6):2776-84. doi: 10.2353/ajpath.2010.090809. Epub 2010 
      Apr 9.