Receptors, Volume 4, Issue 3 (September 2025) – 2 articles

Skeletal muscle aging, or sarcopenia, involves progressive muscle mass and function loss, which limits mobility and independence in elderly populations. This decline is driven by chronic inflammation, oxidative stress, and insulin resistance, all of which impair muscle regeneration and accelerate protein breakdown. Mineralocorticoid receptors (MRs), known for their roles in electrolyte balance, have emerged as key regulators of these processes in skeletal muscle. MR activation promotes inflammatory signaling, increases oxidative stress, and worsens insulin resistance, accelerating sarcopenia progression. This review examines the impact of MRs on muscle health and highlights the therapeutic potential of targeting these receptors to counteract age-related muscle loss. MR antagonists, such as spironolactone, show promise in reducing inflammation and oxidative damage, potentially slowing sarcopenia. Physical exercise, an established intervention for muscle health, may enhance MR antagonism effects by improving insulin sensitivity and reducing inflammation. However, more research is needed to determine the efficacy and safety of combined MR antagonists and exercise protocols for preventing sarcopenia in older adults. Full article

Background: The development of cerebral organoids created from human pluripotent stem cells in 3D culture may greatly improve the discovery of neuropsychiatric medicines. Methods: In the current study we differentiated neural organoids from a human pluripotent stem cell line in vitro, recorded the development of neurophysiological activity using multielectrode arrays (MEAs) and characterized the neuropharmacology of synaptic signaling over 8 months in vitro. In addition, we investigated the ability of these organoids to display epileptiform activity in response to a convulsant agent and the effects of antiseizure medicines to inhibit this abnormal activity. Results: Single and bursts of action potentials from individual neurons and network bursts were recorded on the MEA plates and significantly increased and became more complex from week 7 to week 30, consistent with neural network formation. Neural spiking was reduced by the Na channel blocker tetrodotoxin but increased by the inhibitor of K_V7 potassium channels XE991, confirming the involvement of voltage-gated sodium and potassium channels in action potential activity. The GABA antagonists bicuculline and picrotoxin each increased the spike rate, consistent with inhibitory synaptic signaling. In contrast, the glutamate receptor antagonist kynurenic acid inhibited the spike rate, consistent with excitatory synaptic transmission in the organoids. The convulsant 4-aminopyridine increased spiking, bursts and synchronized firing, consistent with epileptiform activity in vitro. The anticonvulsants carbamazepine, ethosuximide and diazepam each inhibited this epileptiform neural activity. Conclusions: Together, our data demonstrate that neural organoids form inhibitory and excitatory synaptic circuits, generate epileptiform activity in response to a convulsant agent and detect the antiseizure properties of diverse antiepileptic drugs, supporting their value in drug discovery. Full article