Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
Mediators Inflamm. 2018 Sep 27;2018:7219732. doi: 10.1155/2018/7219732. eCollection 2018.
A mild chronic inflammatory state, like that observed in aged individuals, affects microglial function, inducing a dysfunctional phenotype that potentiates neuroinflammation and cytotoxicity instead of neuroprotection in response to additional challenges. Given that inflammatory activation of microglia promotes increased release of D-serine, we postulate that age-dependent inflammatory brain environment leads to microglia-mediated changes on the D-serine-regulated glutamatergic transmission. Furthermore, D-serine dysregulation, in addition to affecting synaptogenesis and synaptic plasticity, appears also to potentiate NMDAR-dependent excitotoxicity, promoting neurodegeneration and cognitive impairment. D-serine dysregulation promoted by microglia could have a role in age-related cognitive impairment and in the induction and progression of neurodegenerative processes like Alzheimer's disease.
一种轻度的慢性炎症状态，如在老年人中观察到的那样，会影响小胶质细胞的功能，诱导一种功能失调的表型，使其在应对额外的挑战时，增强神经炎症和细胞毒性，而不是神经保护。鉴于小胶质细胞的炎症激活促进 D-丝氨酸的释放增加，我们假设，与年龄相关的炎症性大脑环境导致小胶质细胞介导的 D-丝氨酸调节的谷氨酸能传递的变化。此外，D-丝氨酸的失调，除了影响突触发生和突触可塑性外，似乎也增强了 NMDA 受体依赖性兴奋性毒性，促进神经退行性变和认知障碍。小胶质细胞促进的 D-丝氨酸失调可能在与年龄相关的认知障碍以及阿尔茨海默病等神经退行性过程的诱导和进展中发挥作用。
