Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in...

Area of Science:

• Neuroscience
• Hepatology
• Pharmacology

Background:

• Minimal hepatic encephalopathy (MHE) involves cognitive deficits like memory and learning impairments following liver injury.
• The precise neurological mechanisms underlying MHE-associated cognitive dysfunction remain incompletely understood.

Purpose of the Study:

• To investigate the neurological mechanisms of MHE-associated motor learning deficits.
• To explore the role of the glucocorticoid pathway and microglial activation in MHE pathogenesis.

Main Methods:

• A mouse model of MHE was established using repetitive thioacetamide (TAA) administration.
• In vivo 2-photon microscopy was used to observe dendritic spine dynamics in the motor cortex.
• The effects of glucocorticoid receptor blockade and biosynthesis suppression on MHE symptoms were evaluated.

Main Results:

• TAA administration induced hyperammonemia, elevated proinflammatory cytokines, and prominent motor learning deficits in mice.
• MHE mice exhibited excessive dendritic spine pruning in the motor cortex.
• Pharmaceutical inhibition of the glucocorticoid receptor or its biosynthesis ameliorated motor learning deficits and synaptic protein loss.
• Glucocorticoid pathway inhibition also alleviated microglial activation observed in MHE mice.

Conclusions:

• Corticosterone-induced microglial activation and synaptic over-pruning contribute to motor learning impairments in MHE.
• The glucocorticoid pathway represents a potential therapeutic target for MHE treatment.