Hydrogen sulfide and mesenchymal stem cells‐extracted microvesicles attenuate LPS‐induced Alzheimer's disease

Abstract

Both hydrogen sulfide (H2S) and mesenchymal stem cells (MSCs) extracted microvesicles (MVs) are potent anti‐inflammatory molecules. They play an essential role in lowering the production of tumor necrosis factor‐alpha (TNF‐α). The latter could strongly stimulate MiR‐155 that contributes to neurodegeneration and Alzheimer's disease (AD). miR‐155 could repress the expression of inositol 5‐phosphatase‐1 (SHIP‐1) leading eventually to activation of Akt kinase and neurofibrillary development in AD. The current study was conducted to evaluate the role of miR‐155 in a rat model of lipopolysaccharide (LPS)‐induced AD and to investigate the effect of using MVs and H2S that were given either separately or combined in regulating pro‐inflammatory signaling. Thirty female Wistar albino rats aged 6 months to 1 year were equally divided into five groups; control group, LPS‐induced AD group, LPS + MVs group, LPS + NaHS group, and LPS + MVs and NaHS group. The increased miR‐155 level was associated with decreased SHIP‐1 level and positively correlated with TNF‐α. In addition, treatment with MVs and/or NaHS resulted in attenuation of inflammation, decreasing miR‐155, pAkt levels, and downregulation of apoptosis along with improvement of the hippocampal and cortical histopathological alterations. LPS enhanced production of malondialdehyde (MDA) and reduced glutathione (GSH) levels indicating oxidative stress‐induced neural damage, whereas MVs and NaHS could mitigate oxidative damage and accelerate antioxidant capacity via increasing catalase enzyme. In conclusion, downregulation of TNF‐α, miR‐155, and pAkt and increased SHIP‐1 could improve the neuro‐inflammatory state and cognitive function of LPS‐induced Alzheimer's disease.

MiR-155: An Important Regulator of Neuroinflammation

“…The action of other anti-inflammatory molecules on miR-155 expression has been investigated, such as hydrogen sulfide (H 2 S) and microvesicles extracted from mesenchymal stem cells (MSC). AD was induced in albino Wistar rats by intraperitoneal injection of LPS; monotherapy treatment reduced miR-155 levels and inflammation, decreased apoptosis and improved histopathological alterations of the hippocampus [ 65 ].…”

Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

“…Proteins from brain tissues were extracted using a protein extraction kit. Proteins were extracted by using lysis buffer (radioimmunoprecipitation assay (RIPA) buffer with protease and phosphatase inhibitor) on ice for 30 min in a shaker as it was previously done in Aboulhoda et al, (2021), After centrifugation of the tissues at 16,000 g for 30 min at 4℃, the debris was removed. Then, the supernatants were transferred to other tubes for concentration determination and protein analysis.…”

Differential Expression of miR-381-3p in Alzheimer’s Disease Patients and Its Role in Beta-Amyloid-Induced Neurotoxicity and Inflammation

“…For example, Adriane D et al [6] used a high-throughput microarray platform and microarray technology to study the expression changes of mi­RNAs in patients with AD, and 6 miRNAs were identified to be aberrantly expressed in the temporal gyrus of patients. Also, in the basic experimental study, similar changes of miRNAs have been observed in AD mice or cell models, such as miR-331-3p and miR-155 [7, 8]. miR-381-3p is a tumor suppressor molecule that plays an important role in a variety of tumors [9, 10].…”