Faculty Articles

Alterations in Doublecortin Expression in Human Neuronal Stem Cells in Response to Angiotensinergic Stimulation in Proliferation and Differentiation Conditions

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The FASB Journal


Activation or inhibition of the renin-angiotensin system (RAS) affects neuronal function and viability. We showed previously that AT2 selective stimulation of human neuronal stem cells (H-9 derived, Life Technologies) increased cell numbers in both differentiation and proliferation medium compared to control and AT1 stimulated human neuronal stem cells. We now show that doublecortin expression in human neuronal stem cells which were seeded in chamber slides and cultured under proliferation (with EGF and FGF-2) or differentiation (no added growth factors) conditions is altered with chronic exposure to AT1 and AT2 selective agonists. Conditions included 14 days treatment with once daily addition of the AT2 selective agonist CGP42112 (final concentration 100 nM); once daily treatment with the non-selective Ang II receptor agonist Sar1 angiotensin II (100 nM) plus the AT2 receptor selective antagonist PD123319 (10 μM) for selective AT1 receptor stimulation; once daily treatment with PD123319 (10 μM) alone; or once daily treatment with vehicle. Following treatment, cells were immunostained for the neuroblast marker doublecortin. Doublecortin expression was reduced by AT1 selective stimulation in differentiation conditions relative to control (Control 70.9 ± 17% and AT1 14.0 ± 6.2%, p

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