Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease

Abstract

The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD). However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model. Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice. Increased GFAP expression could be associated with the elevation in number of reactive astrocytes. IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found up-regulated in APP/PS1 mice compared to Wild type mice. Furthermore, CCR5 expression was decreased and both CCL3 and CCL4 chemokines were highly expressed indicating a possible gliosis and probably an increase in chemotaxis from lymphocytes and T cell generation. We also noted for the first time, a CCR8 increase expression with diminution of its CCL1 chemokine, both normally involved in protection from bacterial infection and demyelination. Control of inflammatory proteins will be the next step in understanding the progression of AD and also in determining the mechanisms that can develop in this disease.

Astrocytes and Inflammatory Processes in Alzheimer’s Disease

“…These findings imply that neuroinflammation in reactive astrocytes expresses higher levels of APP than when mice are at rest and they, therefore, may end up producing more β amyloid. Similarly, in APP/PS1 mice, an increase in chemokines and their receptors, compared to wild type mice, such as CCL3, CCL4, CCL1 and the receptors CCR5 and CCR8 was detected [108].…”

“…Other studies performed in older mice that overexpress TGFβ in astrocytes promoted the deposition of Aβ, and those astrocytes containing TGFβ1 were located in the vicinity of the Aβ deposits in those mice that overexpressed APP with Swedish mutation [126][127][128][129]. Finally, astrocytes release purines that can influence the development of AD and activate the production of inflammatory proteins, decreasing anti-inflammatory proteins [108].…”

“…Astrocytes can sometimes release reactive oxygen species (ROS), chemokines, or cytokines (CCL3, CCL4, CCL1, IL-1, for example) [108,109]. Normally, those responsible for expressing these substances are going to be the so-called reactive astrocytes that cause functional changes by the expression of genes and the formation of glial scars that can be beneficial [81] or harmful to cells [82].…”

“…The neurotransmitter glutamate is released by astrocytes in the presence of Aβ and can cause neuronal loss as well as synaptic damage by activation of NMDA receptors [154,155]. In addition, astrocytes release purines that can influence the development of AD and activate the production of inflammatory proteins, decreasing anti-inflammatory proteins, such as PPAR-γ [108,156]. This is probably due to the effect of reactive astrogliosis that may have beneficial effects [82] or detrimental effects [83] for neurons, and because these two different reactions depend on the type of triggering of the astrogliosis.…”

Improvement of cognitive and motor performance with mitotherapy in aged mice

“…Rotarod test was operated in a rotarod apparatus (Chengdu Taimeng Biotechnology Co., Ltd., Chengdu, China) consisted of a rotating rod, and five individual compartment that was able to test five mice simultaneously [46]. Mice were placed on a rod that accelerated smoothly from 5 to 20 rpm throughout 120 s. The time that each animal stayed on the rod was recorded as the latent period.…”