Abstract
Chronic glial activation is characterized by increased numbers of activated glial cells, secreting free radicals and cytotoxic cytokines, subsequently causing neuronal damage. In order to investigate the anti-inflammatory activity of Longvida® Optimised Curcumin (LC), we fed 500 ppm of LC to 2-month-old wild type and GFAP-IL6 mice for 6 months. LC feeding led to a significant reduction in the number of Iba-1+ microglia by 26% in the hippocampus and by 48% in the cerebellum, GFAP+ astrocytes by 30%, and TSPO+ cells by 24% in the hippocampus and by 31% in the cerebellum of the GFAP-IL6 mice. The morphology of the cells was assessed and LC significantly decreased the dendritic length of microglia and the convex area, convex perimeter, dendritic length, nodes and number of processes of astrocytes in the hippocampus while decreasing the soma area and perimeter in the cerebellum, in LC-fed GFAP-IL6 mice. In addition, LC feeding increased pre- and postsynaptic protein levels and improved balance measured by Rotarod. Together, these data suggest that LC is able to attenuate the inflammatory pathology and ameliorate neurodegeneration and motor deficits in GFAP-IL6 mice. For patients with neuro-inflammatory disorders, LC might potentially reverse the detrimental effects of chronic glial activation.
Highlights
® anti-inflammatory activity of Longvida Optimised Curcumin (LC), we fed 500 ppm of LC to 2-monthold wild type and glial fibrillary acidic protein (GFAP)-IL6 mice for 6 months
To further support the role of neuroinflammation in Alzheimer’s disease (AD), genome-wide association studies have identified a variety of inflammation-relevant genes that are associated with AD including clusterin (CLU), complement receptor 1 (CR1) and triggering receptor expressed on myeloid cells 2 (TREM2)[7]
While it has been suggested that cytokine-suppressive anti-inflammatory drugs (CSAIDs) such as curcumin are able to downregulate chronic glial activation and protect against inflammation-induced neuronal damage in AD31, there have been relatively few investigations on how CSAIDs could potentially reduce chronic neuroinflammatory processes in preclinical settings
Summary
® anti-inflammatory activity of Longvida Optimised Curcumin (LC), we fed 500 ppm of LC to 2-monthold wild type and GFAP-IL6 mice for 6 months. LC feeding increased pre- and postsynaptic protein levels and improved balance measured by Rotarod Together, these data suggest that LC is able to attenuate the inflammatory pathology and ameliorate neurodegeneration and motor deficits in GFAP-IL6 mice. Microglia are designated as “resting” while the reactive morphology is termed “activated.” Under physiological conditions, microglial shows long, delicate branched processes oriented radially to a small elliptical soma. They are never in a real resting state and play a critical constitutive role in scanning the environment[8]. Iba-1 is a microglia/macrophage specific calcium binding protein, while TSPO is a mitochondrial translocator protein predominantly expressed in the microglia, astrocytes, and macrophages in the blood vessels in the nervous system, in the outer mitochondrial membrane of injured or activated cells[12,13,14]
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