PMID- 25451296
OWN - NLM
STAT- MEDLINE
DCOM- 20151230
LR  - 20211203
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 284
DP  - 2015 Jan 22
TI  - Evidence for the contribution of adult neurogenesis and hippocampal cell death in 
      experimental cerebral malaria cognitive outcome.
PG  - 920-933
LID - S0306-4522(14)00934-8 [pii]
LID - 10.1016/j.neuroscience.2014.10.062 [doi]
AB  - Cognitive dysfunction is a major sign of cerebral malaria (CM). However, the 
      underlying mechanisms of CM cognitive outcome remain poorly understood. A body of 
      evidence suggests that adult neurogenesis may play a role in learning and memory 
      processes. It has also been reported that these phenomena can be regulated by the 
      immune system. We hypothesized that memory dysfunction in CM results from 
      hippocampal neurogenesis impairment mediated by the deregulated immune response 
      during the acute phase of CM. C57Bl/6 mice were infected with Plasmodium berghei 
      ANKA (PbA) strain, using a standardized inoculation of 10(6) parasitized 
      erythrocytes. Long-term working memory was evaluated using the novel object 
      recognition test. The mRNA expression of brain-derived neurotrophic factor 
      (BDNF), tropomyosin-receptor-kinase (TRK-B) and nerve growth factor (NGF) in the 
      frontal cortex and hippocampus was estimated by real-time polymerase chain 
      reaction (PCR). The protein levels of cytokine interleukin-2 (IL-2), IL-4, IL-6, 
      IL-10, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and CCL11 and 
      neurotrophins BDNF and NGF were determined using a cytometric bead array (CBA) 
      kit or enzyme-linked immunosorbent assay. Cell viability in the hippocampus was 
      analyzed by Confocal Microscopy. Neurogenesis in the dentate gyrus was determined 
      through quantification of doublecortin (DCX) positive cells. PbA-infected mice 
      presented working memory impairment on day 5 post-infection. At this same time 
      point, CM mice exhibited a decrease in DCX-positive cells in the dentate gyrus in 
      parallel with increased cell death and elevated inflammatory cytokines (IL-6, 
      TNF-alpha, IFN-gamma and CCL11) in the hippocampus and frontal cortex. A significant 
      reduction of BDNF mRNA expression was also found. IL-6 and TNF-alpha correlated 
      negatively with BDNF and NGF levels in the hippocampus of CM mice. In summary, we 
      provide further evidence that neuroinflammation following PbA-infection 
      influences neurotrophin expression, impairs adult hippocampal neurogenesis and 
      increases hippocampal cell death in association with memory impairment following 
      CM course. The current study identified potential mediators of memory impairment 
      in CM.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - de Miranda, A S
AU  - de Miranda AS
AD  - Postgraduate Program in Health Sciences: Infectious Diseases and Tropical 
      Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, 
      MG, Brazil; Immunopharmacology Group, Department of Biochemistry and Immunology, 
      Institute of Biological Sciences, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil; Neuroscience Branch, Interdisciplinary Laboratory of 
      Medical Investigation, School of Medicine, Federal University of Minas Gerais, 
      Belo Horizonte, MG, Brazil; Neuroinflammation Research Center, Department of 
      Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 
      Electronic address: mirandas.aline@gmail.com.
FAU - Brant, F
AU  - Brant F
AD  - Postgraduate Program in Health Sciences: Infectious Diseases and Tropical 
      Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, 
      MG, Brazil; Immunopharmacology Group, Department of Biochemistry and Immunology, 
      Institute of Biological Sciences, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil.
FAU - Campos, A C
AU  - Campos AC
AD  - Postgraduate Program in Health Sciences: Infectious Diseases and Tropical 
      Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, 
      MG, Brazil; Immunopharmacology Group, Department of Biochemistry and Immunology, 
      Institute of Biological Sciences, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil.
FAU - Vieira, L B
AU  - Vieira LB
AD  - Department of Pharmacology, Institute of Biological Sciences, Federal University 
      of Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Rocha, N P
AU  - Rocha NP
AD  - Immunopharmacology Group, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 
      Brazil; Neuroscience Branch, Interdisciplinary Laboratory of Medical 
      Investigation, School of Medicine, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil; Department of Pharmacology, Institute of Biological 
      Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Cisalpino, D
AU  - Cisalpino D
AD  - Department of Microbiology, Institute of Biological Sciences, Federal University 
      of Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Binda, N S
AU  - Binda NS
AD  - National Institute of Science and Technology in Molecular Medicine, School of 
      Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Rodrigues, D H
AU  - Rodrigues DH
AD  - Immunopharmacology Group, Department of Biochemistry and Immunology, Institute of 
      Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, 
      Brazil; Neuroscience Branch, Interdisciplinary Laboratory of Medical 
      Investigation, School of Medicine, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil.
FAU - Ransohoff, R M
AU  - Ransohoff RM
AD  - Neuroinflammation Research Center, Department of Neuroscience, Lerner Research 
      Institute, Cleveland Clinic, Cleveland, OH, USA.
FAU - Machado, F S
AU  - Machado FS
AD  - Postgraduate Program in Health Sciences: Infectious Diseases and Tropical 
      Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, 
      MG, Brazil; Immunopharmacology Group, Department of Biochemistry and Immunology, 
      Institute of Biological Sciences, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil.
FAU - Rachid, M A
AU  - Rachid MA
AD  - Department of Pathology, Institute of Biological Sciences, Federal University of 
      Minas Gerais, Belo Horizonte, MG, Brazil.
FAU - Teixeira, A L
AU  - Teixeira AL
AD  - Postgraduate Program in Health Sciences: Infectious Diseases and Tropical 
      Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, 
      MG, Brazil; Immunopharmacology Group, Department of Biochemistry and Immunology, 
      Institute of Biological Sciences, Federal University of Minas Gerais, Belo 
      Horizonte, MG, Brazil; Neuroscience Branch, Interdisciplinary Laboratory of 
      Medical Investigation, School of Medicine, Federal University of Minas Gerais, 
      Belo Horizonte, MG, Brazil. Electronic address: altexr@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141113
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (Dcx protein, mouse)
RN  - 0 (Doublecortin Protein)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Death/*physiology
MH  - Cognition Disorders/pathology/*physiopathology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Doublecortin Protein
MH  - Female
MH  - Frontal Lobe/pathology/physiopathology
MH  - Hippocampus/pathology/*physiopathology
MH  - Malaria, Cerebral/pathology/*physiopathology
MH  - Memory Disorders/pathology/physiopathology
MH  - Mice, Inbred C57BL
MH  - Neurogenesis/*physiology
MH  - *Plasmodium berghei
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/metabolism
OTO - NOTNLM
OT  - CCL11
OT  - cerebral malaria
OT  - cognitive dysfunction
OT  - cytokines
OT  - neuroinflammation
OT  - neurotrophin
EDAT- 2014/12/03 06:00
MHDA- 2015/12/31 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/08/26 00:00 [received]
PHST- 2014/10/09 00:00 [revised]
PHST- 2014/10/27 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/12/31 06:00 [medline]
AID - S0306-4522(14)00934-8 [pii]
AID - 10.1016/j.neuroscience.2014.10.062 [doi]
PST - ppublish
SO  - Neuroscience. 2015 Jan 22;284:920-933. doi: 10.1016/j.neuroscience.2014.10.062. 
      Epub 2014 Nov 13.