Immunity impacts cognitive deficits across neurological disorders.
Benjamin C ShawVictoria R AndersRachel A TinkeyMaria L HabeanOrion D BrockBenjamin J FrostinoJessica L WilliamsPublished in: Journal of neurochemistry (2023)
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.
Keyphrases
- traumatic brain injury
- major depressive disorder
- multiple sclerosis
- induced apoptosis
- rheumatoid arthritis
- cell cycle arrest
- patient safety
- poor prognosis
- oxidative stress
- quality improvement
- mass spectrometry
- end stage renal disease
- cognitive impairment
- ms ms
- mild cognitive impairment
- chronic kidney disease
- cell death
- physical activity
- spinal cord
- depressive symptoms
- spinal cord injury
- white matter
- inflammatory response
- binding protein
- long non coding rna