PMID- 29471842
OWN - NLM
STAT- MEDLINE
DCOM- 20190409
LR  - 20240216
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 15
IP  - 1
DP  - 2018 Feb 23
TI  - Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer's disease 
      in wild-type, C57BL/6 mice.
PG  - 57
LID - 10.1186/s12974-018-1086-8 [doi]
LID - 57
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease 
      associated with cognitive decline and complete loss of basic functions. The 
      ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one 
      third of the world's population and is implicated in AD. METHODS: We infected 
      C57BL/6 wild-type male and female mice with 10 T. gondii ME49 cysts and assessed 
      whether infection led to behavioral and anatomical effects using 
      immunohistochemistry, immunofluorescence, Western blotting, cell culture assays, 
      as well as an array of mouse behavior tests. RESULTS: We show that T. gondii 
      infection induced two major hallmarks of AD in the brains of C57BL/6 male and 
      female mice: beta-amyloid (Abeta) immunoreactivity and hyperphosphorylated Tau. 
      Infected mice showed significant neuronal death, loss of N-methyl-D-aspartate 
      receptor (NMDAR) expression, and loss of olfactory sensory neurons. T. gondii 
      infection also caused anxiety-like behavior, altered recognition of social 
      novelty, altered spatial memory, and reduced olfactory sensitivity. This last 
      finding was exclusive to male mice, as infected females showed intact olfactory 
      sensitivity. CONCLUSIONS: These results demonstrate that T. gondii can induce 
      advanced signs of AD in wild-type mice and that it may induce AD in some 
      individuals with underlying health problems.
FAU - Torres, Luisa
AU  - Torres L
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 14853, USA.
FAU - Robinson, Sudie-Ann
AU  - Robinson SA
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 14853, USA.
FAU - Kim, Do-Geun
AU  - Kim DG
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 14853, USA.
FAU - Yan, Angela
AU  - Yan A
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 14853, USA.
FAU - Cleland, Thomas A
AU  - Cleland TA
AD  - Department of Psychology, Cornell University, Ithaca, NY, 14853, USA.
FAU - Bynoe, Margaret S
AU  - Bynoe MS
AD  - Department of Microbiology and Immunology, College of Veterinary Medicine, 
      Cornell University, Ithaca, NY, 14853, USA. msb76@cornell.edu.
LA  - eng
GR  - R01 NS063011/NS/NINDS NIH HHS/United States
GR  - R01 NS063011/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20180223
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Alzheimer Disease/etiology/*metabolism/*parasitology
MH  - Animals
MH  - Cells, Cultured
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Random Allocation
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Signal Transduction/*physiology
MH  - *Toxoplasma
MH  - Toxoplasmosis/complications/*metabolism
PMC - PMC5824585
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid beta
OT  - NMDAR
OT  - Olfactory sensory neurons
OT  - Toxoplasma gondii
COIS- ETHICS APPROVAL: All animal work was done in accordance with PHS guidelines and 
      was approved by Cornell's Institutional Animal Care and Use Committee (Protocol # 
      2008-0092). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The 
      authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer 
      Nature remains neutral with regard to jurisdictional claims in published maps and 
      institutional affiliations.
EDAT- 2018/02/24 06:00
MHDA- 2019/04/10 06:00
PMCR- 2018/02/23
CRDT- 2018/02/24 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/02/01 00:00 [accepted]
PHST- 2018/02/24 06:00 [entrez]
PHST- 2018/02/24 06:00 [pubmed]
PHST- 2019/04/10 06:00 [medline]
PHST- 2018/02/23 00:00 [pmc-release]
AID - 10.1186/s12974-018-1086-8 [pii]
AID - 1086 [pii]
AID - 10.1186/s12974-018-1086-8 [doi]
PST - epublish
SO  - J Neuroinflammation. 2018 Feb 23;15(1):57. doi: 10.1186/s12974-018-1086-8.