Chapter 15 - Neuroinflammation

Abstract

Neuroinflammation is implicated in contributing to a variety of neurologic and somatic illnesses including Alzheimer's disease (AD), Parkinson's disease (PD), and depression. In this chapter, we focus on the role of neuroinflammation in mediating these three illnesses and portray interactions between the immune response and the central nervous system in the context of sex differences in disease progression. The majority of this chapter is supported by clinical findings; however, we occasionally utilize preclinical models where human studies are currently lacking. We begin by detailing the pathology of neuroinflammation, distinguishing between acute and chronic inflammation, and examining contributions from the innate and adaptive immune systems. Next, we summarize potential mechanisms of immune cell mediators including interleukin-1 beta (IL-1β), tumor necrosis factor α, and IL-6 in AD, PD, and depression development. Given the strong sex bias seen in these illnesses, we additionally examine the role of sex hormones, e.g., estrogen and testosterone in mediating neuroinflammation at the cellular level. Systematically, we detail how sex hormones may contribute to distinct behavioral and clinical symptoms and prognosis between males and females with AD, PD, or depression. Finally, we highlight the possible role of exercise in alleviating neuroinflammation, as well as evidence that antiinflammatory drug therapies improve cognitive symptoms observed in brain-related diseases.