Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice.
BACKGROUND
Because the outcomes and sequelae after different types of brain injury (BI) are variable and difficult to predict, investigations on whether enhanced expressions of BI-associated biomarkers (BIABs), including transforming growth factor beta1 (TGF-beta1), S100B, glial fibrillary acidic protein (GFAP), neurofilament light chain (NF-L), tissue transglutaminases (tTGs), beta-amyloid precursor proteins (AbetaPP), and tau are present as well as whether impairment of the ubiquitin-proteasome system (UPS) is present have been widely used to help delineate pathophysiological mechanisms in various BIs. Larvae of Toxocara canis can invade the brain and cause BI in humans and mice, leading to cerebral toxocariasis (CT). Because the parasitic burden is light in CT, it may be too cryptic to be detected in humans, making it difficult to clearly understand the pathogenesis of subtle BI in CT. Since the pathogenesis of murine toxocariasis is very similar to that in humans, it appears appropriate to use a murine model to investigate the pathogenesis of CT.


METHODS
BIAB expressions and UPS function in the brains of mice inoculated with a single dose of 250 T. canis embryonated eggs was investigated from 3 days (dpi) to 8 weeks post-infection (wpi) by Western blotting and RT-PCR.


RESULTS
Results revealed that at 4 and 8 wpi, T. canis larvae were found to have invaded areas around the choroid plexus but without eliciting leukocyte infiltration in brains of infected mice; nevertheless, astrogliosis, an indicator of BI, with 78.9~142.0-fold increases in GFAP expression was present. Meanwhile, markedly increased levels of other BIAB proteins including TGF-beta1, S100B, NF-L, tTG, AbetaPP, and tau, with increases ranging 2.0~12.0-fold were found, although their corresponding mRNA expressions were not found to be present at 8 wpi. Concomitantly, UPS impairment was evidenced by the overexpression of conjugated ubiquitin and ubiquitin in the brain.


CONCLUSIONS
Further studies are needed to determine whether there is an increased risk of CT progression into neurodegenerative disease because neurodegeneration-associated AbetaPP and phosphorylated tau emerged in the brain.
Institute of Tropical Medicine, National Yang-Ming University School of Medicine, 155 Li-Nong St,, Sec, 2, Taipei 112, Taiwan. toxoplasma0422@yahoo.com.tw
Chien-Wei
CW
Liao
Chia-Kwung
CK
Fan
Ting-Chang
TC
Kao
Dar-Der
DD
Ji
Kua-Eyre
KE
Su
Yun-Ho
YH
Lin
Wen-Long
WL
Cho
D000818:Animals; D000909:Antibodies, Helminth; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D020809:Central Nervous System Helminthiasis / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein; D007814:Larva; D051379:Mice; D009414:Nerve Growth Factors / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis; D016900:Neurofilament Proteins / Q000032:analysis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis; D017166:Toxocara canis / Q000276:immunology / Q000472:pathogenicity*; D014120:Toxocariasis / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D011503:Transglutaminases / Q000032:analysis; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000032:analysis
D000909:Antibodies, Helminth; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; D053773:Transforming Growth Factor beta1; D025801:Ubiquitin; C528900:glial fibrillary astrocytic protein, mouse; C044882:neurofilament protein L; D016875:tau Proteins; D011503:Transglutaminases; C119272:beta-amyloid precursor protein kinase I; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex