Hypoxic-conditioned medium from adipose tissue mesenchymal stem cells improved neuroinflammation through alternation of toll like receptor (TLR) 2 and TLR4 expression in model of Alzheimer's disease rats.

Microglia have a pivotal role to initiate immune responses in AD brains through toll-like receptors and induce neuroinflammation. Adipose tissue mesenchymal stem cells (ATSCs) secret many neurotrophic and anti-inflammatory factors called conditioned medium (CM). Many studies have demonstrated that CM of mesenchymal stem cells facilitate regeneration and attenuates inflammation in many disorders. To this purpose, the effect of ATSCs-conditioned medium (ATSC-CM) on brain inflammation and the role of toll-like receptors were investigated in this study. Seventy-two rats were randomly divided into 6 groups: control, sham, sham+ATSC-CM: 200μl ATSC-CM once a day intraperitoneally for 8 days, AD group injected the Aβ1-40 intra-hippocampal, AD+ASC-CM, which was injected Aβ1-40 intra-hippocampal and 200μl ATSC-CM once a day intraperitoneally for 8 days and AD+ rivastigmine: was injected Aβ1-40 intra-hippocampal and received rivastigmine (0.6 mg/kg) orally once a day for 2 weeks. Memory and learning were measured by Morris water maze and novel object recognition tests. For detection of beta-amyloid plaque, Congo red staining was used, and neuronal survival was assessed by Nissl staining. Expression of TLR2 and TLR4 was measured by real-time PCR, and finally, to assess inflammation markers (IL-1β and TNF-α) in the hippocampus, ELISA kits were used. In treatment group spatial and recognition memory significantly was improved. ATSC-CM administration decreased beta amyloid plaques and enhanced neuronal survival in AD brain rats. In addition, TLR2 and TLR4 expression decreased in treatment group. Results also showed that ATSC-CM reduced IL-1β and TNF-α as inflammation markers. ATSC-CM improved memory deficit, decreased beta amyloids formation, increased neuron survival, and attenuated inflammation by reducing the expression of TLRs.