Can<i>Toxoplasma gondii</i>Pave the Road for Dementia?
Enas A. El Saftawy, N. Amin, Rania Mohamed Sabry, Noha El‐Anwar, Rania Y. Shash, Eman Hany Elsebaie, Rita Wassef
Abstract
Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii ( T. gondii) . The long-term sequels of anti- Toxoplasma premunition, chiefly dominated by TNF- α , on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF- α signaling pathway induces NF- κβ that may induce or inhibit neurogenesis. This study speculates the potential impact of anti- Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF- α serum levels, the in situ expression of NF- κβ , and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF- α serum level (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi></mml:math>value ≤ 0.004) and significant upsurge in NF- κβ whereas IGF-1R was of low abundance (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi></mml:math>value < 0.05) compared to the controls. TNF- α had a strong positive correlation with the intracerebral expression of NF- κβ (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>r</mml:mi></mml:math>value ≈ 0.943,<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi></mml:math>value ≈ 0.005) and a strong negative correlation to IGF-1R (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>r</mml:mi></mml:math>value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF- α /NF- κβ keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor’s ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.