One example is, Lanz et al. plainly demonstrated that angiotensin II acts as being a paracrine mediator, sustaining inammation in the CNS by way of TGF B upregulation in astrocytes, We also reported that aldosterone secretion induced by angiotensin II in astrocytes enhances neuronal injury due to angiotensin II, Furthermore, Liu et al. showed that angiotensin II induces astrocyte senescence by means of superoxide production, These ndings of astrocyte dysfunction induced by angiotensin II also make clear the essential position of angiotensin II in dysfunction from the neurovascular unit, The key actions of angiotensin II are mediated through the AT1 receptor, whereas the position of a 2nd receptor subtype referred to as the angiotensin II style 2 receptor is suggested to be guarding of your brain, In the brain, AT2 receptors are expressed not only within the vascular wall but additionally in parts relevant to understanding and manage of motor exercise, Mice with deletion of the AT2 receptor had been reported to exhibit worse cognitive perform compared with wild type selleck inhibitor mice, Reinecke et al.
demonstrated the probability that stimulation within the AT2 receptor could possibly encourage cell dierentiation and regeneration in neuronal tissue and that AT2 receptor stimulation supported neuronal survival and neurite outgrowth in response to ischemia induced selleck chemical AG-1478 neuronal damage, We also demonstrated that AT2 receptor signaling enhanced neural dierentiation plus the fix of damaged DNA by induction of the neural dierentiating factor, methyl methanesulfonate delicate two, that’s 1 of your ubiquitin conjugating enzyme variants, In addition, Gallo Payet et al. reported that angiotensin II induces neural dierentiation and neurite outgrowth by way of mitogen activated protein kinase or nitric oxide through AT2 receptor activation, and it is involved in cerebellar development, Hence, direct AT2 receptor stimulation is expected to have a benecial eect on cognitive perform.
We examined the probability that direct stimulation of your AT2 receptor by a newly created direct AT2 receptor agonist, Compound 21, would improve cognitive function, Each day intraperitoneal

injection of C21 for two weeks signicantly enhanced spatial studying evaluated from the Morris water maze check in C57BL6 mice, but this eect was not observed in AT2 receptor decient mice. C21 treatment greater cerebral blood ow assessed by laser speckle owmetry and hippocampal eld excitatory postsy naptic probable. Also, treatment with C21 prevented cognitive decline in an Alzheimer disease mouse model with intracerebroventricular injection of amyloid B, AT2 receptor activation is reported to stimulate the release of NOcGMP and may possibly mediate vascular relaxation and blood ow indirectly by means of modulation of bradykinin release, In our model, C21 induced cognitive enhancement was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist.