Shaw Benjamin C, Anders Victoria R, Tinkey Rachel A, Habean Maria L, Brock Orion D, Frostino Benjamin J, Williams Jessica L
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
J Neurochem. 2024 Oct;168(10):3512-3535. doi: 10.1111/jnc.15999. Epub 2023 Oct 29.
Cognitive deficits are a common comorbidity with neurological disorders and normal aging. Inflammation is associated with multiple diseases including classical neurodegenerative dementias such as Alzheimer's disease (AD) and autoimmune disorders such as multiple sclerosis (MS), in which over half of all patients experience some form of cognitive deficits. Other degenerative diseases of the central nervous system (CNS) including frontotemporal lobe dementia (FTLD), and Parkinson's disease (PD) as well as traumatic brain injury (TBI) and psychological disorders like major depressive disorder (MDD), and even normal aging all have cytokine-associated reductions in cognitive function. Thus, there is likely commonality between these secondary cognitive deficits and inflammation. Neurological disorders are increasingly associated with substantial neuroinflammation, in which CNS-resident cells secrete cytokines and chemokines such as tumor necrosis factor (TNF)α and interleukins (ILs) including IL-1β and IL-6. CNS-resident cells also respond to a wide variety of cytokines and chemokines, which can have both direct effects on neurons by changing the expression of ion channels and perturbing electrical properties, as well as indirect effects through glia-glia and immune-glia cross-talk. There is significant overlap in these cytokine and chemokine expression profiles across diseases, with TNFα and IL-6 strongly associated with cognitive deficits in multiple disorders. Here, we review the involvement of various cytokines and chemokines in AD, MS, FTLD, PD, TBI, MDD, and normal aging in the absence of dementia. We propose that the neuropsychiatric phenotypes observed in these disorders may be at least partially attributable to a dysregulation of immunity resulting in pathological cytokine and chemokine expression from both CNS-resident and non-resident cells.
认知缺陷是神经疾病和正常衰老中常见的共病情况。炎症与多种疾病相关，包括经典的神经退行性痴呆，如阿尔茨海默病（AD），以及自身免疫性疾病，如多发性硬化症（MS），其中超过一半的患者会出现某种形式的认知缺陷。其他中枢神经系统（CNS）退行性疾病，包括额颞叶痴呆（FTLD）、帕金森病（PD）以及创伤性脑损伤（TBI）和心理障碍，如重度抑郁症（MDD），甚至正常衰老，都存在细胞因子相关的认知功能下降。因此，这些继发性认知缺陷与炎症之间可能存在共性。神经疾病越来越多地与大量神经炎症相关，其中中枢神经系统驻留细胞会分泌细胞因子和趋化因子，如肿瘤坏死因子（TNF）α和白细胞介素（ILs），包括IL-1β和IL-6。中枢神经系统驻留细胞也会对多种细胞因子和趋化因子做出反应，这些因子可通过改变离子通道表达和扰乱电特性对神经元产生直接影响，以及通过神经胶质细胞间和免疫-神经胶质细胞间的相互作用产生间接影响。这些细胞因子和趋化因子的表达谱在各种疾病中存在显著重叠，TNFα和IL-6与多种疾病中的认知缺陷密切相关。在此，我们综述了各种细胞因子和趋化因子在AD、MS、FTLD、PD、TBI、MDD以及无痴呆的正常衰老中的作用。我们提出，在这些疾病中观察到的神经精神表型可能至少部分归因于免疫失调，导致中枢神经系统驻留和非驻留细胞出现病理性细胞因子和趋化因子表达。
