Immune Activation in Brain Aging and Neurodegeneration: Too Much or Too Little?

Abstract

Until recently the brain was studied almost exclusively by neuroscientists and the immune system by immunologists, fuelling the notion that these systems represented two isolated entities. However, as more data suggest an important role of the immune system in regulating the progression of brain aging and neurodegenerative disease, it has become clear that the crosstalk between these systems can no longer be ignored and a new interdisciplinary approach is necessary. A central question that emerges is whether immune and inflammatory pathways become hyperactivated with age and promote degeneration or whether insufficient immune responses, which fail to cope with age-related stress may contribute to disease. We try to explore here the consequences of gain- versus loss-of-function with an emphasis on microglia as sensors and effectors of immune function in the brain and we discuss the potential role of the peripheral environment in neurodegenerative diseases.

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…This spatial organization within the brain demonstrates how microglia are active surveyors of their tissue microenvironment, sensing the location of other microglia and receiving regulatory signals from surrounding neurons that influence their location. The surface membrane of microglia is replete with a tremendous diversity of receptors for mounting stimulus-specific responses against a variety of potential threats to tissue homeostasis (for review see Hanisch et al, 2007;Lucin and Wyss-Coray, 2009;Ransohoff and Perry, 2009;Saijo and Glass, 2011). This includes an extensive catalog of exogenous factors, such as infectious microbes (eg, bacterial, viral, or fungal pathogens), toxins, and other foreign substances (ie, xenobiotics), as well as noxious endogenous compounds released from dead or dying cells that often result from conditions such as traumatic brain injury, ischemia, or neurodegeneration (Xanthos and Sandkühler, 2014).…”

Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response

“…Moreover, some of the observed effects of microglia entering the brain were suggested to be directly related to the irradiation effects on the blood-brain barrier (Ajami et al, 2007;Lucin and Wyss-Coray, 2009). However, this issue was systematically studied by Turrin et al (2007) who compared the brain expression of innate immune markers in normal, GFP-expressing, and chimeric mice, respectively, upon LPS administration.…”

The effects of aging vs. α7 nAChR subunit deficiency on the mouse brain transcriptome: aging beats the deficiency

“…Interestingly, glial cells of AD patients secreted more C1q than nondemented elderly controls (Lue et al 2001). Moreover, the levels of various complement components increase during the course of neurodegenerative disorders such as AD, PD, Huntington, and prion diseases (reviewed by Lucin and Wyss-Coray 2009). In other aging tissues, such as muscle, lung, thymocytes, and kidney, an increase in immune response genes was also demonstrated (Aoshiba and Nagai 2007; Lustig et al 2009;Rodwell et al 2004;Zahn et al 2006).…”