Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative Proteinopathies

Abstract

The olfactory bulb (OB) shows early neuropathological hallmarks in numerous neurodegenerative diseases, for example, in Alzheimer's disease (AD) and Parkinson's disease (PD). The glomerular and granular cell layer of the OB is characterized by preserved cellular plasticity in the adult brain. In turn, alterations of this cellular plasticity are related to neuroinflammation such as microglia activation, implicated in the pathogenesis of AD and PD, as well as frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1) expressing microglia in the glomerular and granular cell layer, and the olfactory tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies (PDD/DLB), and FTLD compared to age-matched controls. The number of Iba1 and CD68 positive microglia associated with enlarged amoeboid microglia was increased particularly in AD, to a lesser extent in FTLD and PDD/DLB as well, while the proportion of proliferating microglia was not altered. In addition, cells expressing the immature neuronal marker polysialylated neural cell adhesion molecule (PSA-NCAM) were increased in the glomerular layer of PDD/DLB and FTLD cases only. These findings provide novel and detailed insights into differential levels of microglia activation in the OB of neurodegenerative diseases.

Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis

“…Histopathological findings in the olfactory bulb of EAE-affected mice revealed that infiltration of inflammatory cells and subsequent microgliosis were evident; this has also been shown in the olfactory bulb of human MS patients [15], suggesting that olfactory deficits in both human MS and the animal model of EAE are associated with neuroinflammation in the olfactory bulb, a central region of olfaction. Alternatively, reduced migration of progenitor cells to the olfactory bulb has been suggested as a cause of olfactory deficit in EAE-affected mice [26].…”

“…Olfactory dysfunction occurs as a result of axonal degeneration in primary progressive MS patients, and CNS inflammation in relapsing-remitting MS patients [13]. In neurodegenerative diseases, microglial activation in the olfactory bulb is thought to be a consequence of CNS inflammation [1516], which also partially interrupts neural transmission [17]. Microglial activation has been also shown in the olfactory bulb of Niemann-Pick disease type C1 mice [1819].…”

Excessive Expression of Microglia/Macrophage and Proinflammatory Mediators in Olfactory Bulb and Olfactory Dysfunction After Stroke

“…Olfactory dysfunction can be caused by olfactory bulb microglia activation, which can be induced by Alzheimer's, Parkinson's, and Niemann-Pick disease type C (10,21). In a previous study by our group, rats after MCAO had microglia and macrophage activation in the ischemic side of the brain (22).…”

Activation of Dopamine D2 Receptor Alleviates Neuroinflammation and Neuronal Injury in Mice Model of Allergic Rhinitis With Olfactory Dysfunction

“…Actually, microgliosis are representative pathological changes that develop during neuroin ammation of central nervous system (CNS) [2]. A close link between microglial hyperplasia of olfactory bulb and olfactory dysfunction has been reported in the patients and animal models of the neuroimmunological disorders, including experimental autoimmune encephalomyelitis (EAE), Alzheimer's disease (AD) and Parkinson's disease (PD) and so on [3][4][5]. Furthermore, recent studies have shown that airway allergen exposure directly induces neuroin ammation [6,7], such as increased Th2-type cytokines and nNOS in the olfactory bulb of airway in ammation animal models [8,9].…”