Cyclic AMP signaling promotes regeneration of cochlear synapses after excitotoxic or noise trauma.

Introduction: Cochlear afferent synapses connecting inner hair cells to spiral ganglion neurons are susceptible to excitotoxic trauma on exposure to loud sound, resulting in a noise-induced cochlear synaptopathy (NICS). Here we assessed the ability of cyclic AMP-dependent protein kinase (PKA) signaling to promote cochlear synapse regeneration, inferred from its ability to promote axon regeneration in axotomized CNS neurons, another system refractory to regeneration.

Methods: We mimicked NICS by applying a glutamate receptor agonist, kainic acid (KA) to organotypic cochlear explant cultures and experimentally manipulated cAMP signaling to determine whether PKA could promote synapse regeneration.

Identifying targets to prevent aminoglycoside ototoxicity.

Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes.

Prevention of murine lupus nephritis by targeting multiple signaling axes and oxidative stress using a synthetic triterpenoid.

Objective: Current treatment options for lupus are far from optimal. Previously, we reported that phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, MEK-1/ERK-1,2, p38, STAT-3, STAT-5, NF-κB, multiple Bcl-2 family members, and various cell cycle molecules were overexpressed in splenic B cells in an age-dependent and gene dose-dependent manner in mouse strains with spontaneous lupus. Since the synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) has been shown to inhibit AKT, MEK-1/2, and NF-κB, and to induce caspase-mediated apoptosis, we tested the therapeutic potential of this agent in murine lupus nephritis.