The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
Maurice Wohl Basic and Clinical Neuroscience Institute, King's College London, Denmark Hill, London, SE5 9NU, UK.
Sci Rep. 2024 Jun 14;14(1):13749. doi: 10.1038/s41598-024-63464-3.
Prion diseases are fatal, infectious, neurodegenerative disorders resulting from accumulation of misfolded cellular prion protein in the brain. Early pathological changes during CNS prion disease also include reactive astrocyte activation with increased CD44 expression, microgliosis, as well as loss of dendritic spines and synapses. CD44 is a multifunctional cell surface adhesion and signalling molecule which is considered to play roles in astrocyte morphology and the maintenance of dendritic spine integrity and synaptic plasticity. However, the role of CD44 in prion disease was unknown. Here we used mice deficient in CD44 to determine the role of CD44 during prion disease. We show that CD44-deficient mice displayed no difference in their response to CNS prion infection when compared to wild type mice. Furthermore, the reactive astrocyte activation and microgliosis that accompanies CNS prion infection was unimpaired in the absence of CD44. Together, our data show that although CD44 expression is upregulated in reactive astrocytes during CNS prion disease, it is dispensable for astrocyte and microglial activation and the development of prion neuropathogenesis.
朊病毒病是由错误折叠的细胞朊病毒蛋白在大脑中积累引起的致命性、传染性、神经退行性疾病。中枢神经系统朊病毒病的早期病理变化还包括反应性星形胶质细胞激活，CD44 表达增加，小胶质细胞增生，以及树突棘和突触的丢失。CD44 是一种多功能的细胞表面黏附和信号分子，被认为在星形胶质细胞形态以及树突棘完整性和突触可塑性的维持中发挥作用。然而，CD44 在朊病毒病中的作用尚不清楚。在这里，我们使用缺乏 CD44 的小鼠来确定 CD44 在朊病毒病中的作用。我们发现，与野生型小鼠相比，缺乏 CD44 的小鼠在对中枢神经系统朊病毒感染的反应中没有差异。此外，在缺乏 CD44 的情况下，伴随中枢神经系统朊病毒感染的反应性星形胶质细胞激活和小胶质细胞增生并未受损。总之，我们的数据表明，尽管 CD44 在中枢神经系统朊病毒病期间在反应性星形胶质细胞中上调，但它对于星形胶质细胞和小胶质细胞的激活以及朊病毒神经发病机制的发展是可有可无的。
