| First Author | Melkonyan MM | Year | 2017 |
| Journal | Int J Mol Sci | Volume | 19 |
| Issue | 1 | PubMed ID | 29267189 |
| Mgi Jnum | J:352639 | Mgi Id | MGI:7666190 |
| Doi | 10.3390/ijms19010009 | Citation | Melkonyan MM, et al. (2017) Neuroprotective, Neurogenic, and Amyloid Beta Reducing Effect of a Novel Alpha 2-Adrenoblocker, Mesedin, on Astroglia and Neuronal Progenitors upon Hypoxia and Glutamate Exposure. Int J Mol Sci 19(1) |
| abstractText | Locus coeruleus-noradrenergic system dysfunction is known to contribute to the progression of Alzheimer's disease (AD). Besides a variety of reports showing the involvement of norepinephrine and its receptor systems in cognition, amyloid beta (Abeta) metabolism, neuroinflammation, and neurogenesis, little is known about the contribution of the specific receptors to these actions. Here, we investigated the neurogenic and neuroprotective properties of a new alpha2 adrenoblocker, mesedin, in astroglial primary cultures (APC) from C57BL/6 and 3xTg-AD mice. Our results demonstrate that mesedin rescues neuronal precursors and young neurons, and reduces the lactate dehydrogenase (LDH) release from astroglia under hypoxic and normoxic conditions. Mesedin also increased choline acetyltransferase, postsynaptic density marker 95 (PSD95), and Abeta-degrading enzyme neprilysin in the wild type APC, while in the 3xTg-AD APC exposed to glutamate, it decreased the intracellular content of Abeta and enhanced the survival of synaptophysin-positive astroglia and neurons. These effects in APC can at least partially be attributed to the mesedin's ability of increasing the expression of Interleukine(IL)-10, which is a potent anti-inflammatory, neuroprotective neurogenic, and Abeta metabolism enhancing factor. In summary, our data identify the neurogenic, neuroprotective, and anti-amyloidogenic action of mesedin in APC. Further in vivo studies are needed to estimate the therapeutic value of mesedin for AD. |
