Deficiency of t PA Exacerbates White Matter Damage

Deficiency of t. PA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice Yu Peng, Venkat Poornima, Chopp Michael, Zacharek Alex, Shen Yi, Liang Linlin, Landschoot. Ward Julie, Liu Zhongwu, Jiang Rongcai, Chen Jieli 1 Department of Neurosurgery, Tianjin Medical University General Hospital, and Tianjin Neurological institute, Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China. 2 Neurology, Henry Ford Hospital, Detroit, MI, USA. 3 Department of Neurosurgery, Shanghai Tenth People&#x 02019; s Hospital, Tongji University, Shanghai, China. 4 Department of Physics, Oakland University, Rochester, MI, USA. 5 Reproductive Medical Center, Henan Provincial People&#x 02019; s Hospital, Zhengzhou, China Figure 1. Aging and t. PA deficiency induce progressive cognitive deficits ( A ) Significant short-term memory loss evaluated by novel object recognition test is evident in middle-aged WT mice compared to young WT mice, and in young and middle-aged t. PA -/- mice compared to age-matched WT mice. ( B ) Long-term memory deficits evaluated by odor test are evident in middle-aged WT mice compared to young WT mice as well as young, adult Aging and Disease, 2019, 10(4), 770 -783. DOI: 10. 14336/AD. 2018. 0816 and middle-aged t. PA -/- mice compared to corresponding age-matched WT mice. ( C ) Aging decreases t. PA expression level in brain of WT mice. Adult mice (6 m) have significantly lower t. PA expression in brain compared to young mice (3 m), and middle-aged (12 m) mice have significantly lower t. PA levels than young and adult mice. ( D ) t. PA -/- mice and middle-aged WT mice exhibit significantly increased spatial learning and memory deficits measured by Morris Water maze test. &#x 0002 A; p&#x 0003 C; 0. 05, n=6/group.