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Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis.

Abstract Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease.
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Journal Title plos neglected tropical diseases
Publication Year Start




PMID- 28821016
OWN - NLM
STAT- Publisher
DA  - 20170818
LR  - 20170818
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 8
DP  - 2017 Aug 18
TI  - Expression of interferon-inducible chemokines and sleep/wake changes during early
      encephalitis in experimental African trypanosomiasis.
PG  - e0005854
LID - 10.1371/journal.pntd.0005854 [doi]
AB  - BACKGROUND: Human African trypanosomiasis or sleeping sickness, caused by the
      parasite Trypanosoma brucei, leads to neuroinflammation and characteristic
      sleep/wake alterations. The relationship between the onset of these alterations
      and the development of neuroinflammation is of high translational relevance, but 
      remains unclear. This study investigates the expression of interferon (IFN)-gamma
      and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the
      serum and cerebrospinal fluid prior to and during the encephalitic stage of
      trypanosome infection, and correlates these with sleep/wake changes in a rat
      model of the disease. METHODOLOGY/PRINCIPAL FINDINGS: The expression of genes
      encoding IFN-gamma, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats
      infected with Trypanosoma brucei brucei and matched controls using
      semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and
      cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored
      by telemetric recording. Using immunohistochemistry, parasites were found in the 
      brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-gamma,
      Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi
      followed by further increase between 14 and 21 dpi. CXCL10 concentration in the
      cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the
      serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was
      evident at 14 dpi, especially in the phase of wake predominance, with intrusion
      of sleep episodes into wakefulness. CONCLUSIONS/SIGNIFICANCE: The results show a 
      modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of
      sleep/wake cycle fragmentation in the initial encephalitic stage, followed by
      increases in Ifn-gamma and IFN-dependent chemokine transcripts in the brain and
      of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake
      alterations could provide combined humoral and functional biomarkers of the early
      encephalitic stage in African trypanosomiasis.
FAU - Laperchia, Claudia
AU  - Laperchia C
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
FAU - Tesoriero, Chiara
AU  - Tesoriero C
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
FAU - Seke-Etet, Paul F
AU  - Seke-Etet PF
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
FAU - La Verde, Valentina
AU  - La Verde V
AD  - Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
FAU - Colavito, Valeria
AU  - Colavito V
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
FAU - Grassi-Zucconi, Gigliola
AU  - Grassi-Zucconi G
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
FAU - Rodgers, Jean
AU  - Rodgers J
AD  - Institute of Biodiversity, Animal Health & Comparative Medicine, University of
      Glasgow, Glasgow, United Kingdom.
FAU - Montague, Paul
AU  - Montague P
AD  - Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, 
      United Kingdom.
FAU - Kennedy, Peter G E
AU  - Kennedy PGE
AUID- ORCID: http://orcid.org/0000-0002-8420-8583
AD  - Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, 
      United Kingdom.
FAU - Bentivoglio, Marina
AU  - Bentivoglio M
AD  - Department of Neuroscience, Biomedicine and Movement Sciences, University of
      Verona, Verona, Italy.
AD  - National Institute of Neuroscience (INN), Verona Unit, Verona, Italy.
LA  - eng
PT  - Journal Article
DEP - 20170818
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
EDAT- 2017/08/19 06:00
MHDA- 2017/08/19 06:00
CRDT- 2017/08/19 06:00
PHST- 2017/06/08 [received]
PHST- 2017/08/04 [accepted]
AID - 10.1371/journal.pntd.0005854 [doi]
AID - PNTD-D-17-00931 [pii]
PST - aheadofprint
SO  - PLoS Negl Trop Dis. 2017 Aug 18;11(8):e0005854. doi:
      10.1371/journal.pntd.0005854.