Wogonin mitigates microglia-mediated synaptic over-pruning and cognitive impairment following epilepsy
Yang Hu1, Honggang Qi1, Jiurong Yang1
1Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.
Summary
Wogonin, a natural compound, reduces excessive synaptic pruning by microglia in epilepsy, improving cognitive function in mice. This neuroprotective effect is mediated by the AKT/FoxO1 pathway.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Epilepsy involves recurrent neuronal discharges, causing brain dysfunction and significant patient burden.
- Activated microglia in the central nervous system (CNS) can excessively prune synapses, worsening epilepsy-related neuronal damage and cognitive decline.
- Wogonin, a flavonoid, shows neuroprotection, but its effect on microglial activation and synaptic pruning in epilepsy is unknown.
Purpose of the Study:
- To investigate the impact of wogonin on microglial activation, synaptic pruning, and cognitive function in a mouse model of epilepsy.
- To elucidate the molecular mechanisms underlying wogonin's effects, particularly its influence on the AKT/FoxO1 pathway.
Main Methods:
- A pilocarpine-induced epilepsy mouse model was used to assess synaptic density (Synaptophysin, Psd-95) and microglial phagocytosis.
- Wogonin (50 and 100 mg/kg) was administered intraperitoneally, followed by behavioral tests (Y-maze, object recognition, Morris water maze).
- Single-cell sequencing and pathway analysis (AKT/FoxO1) were employed to understand microglial state alterations.
Main Results:
- Epileptic mice showed activated microglia with increased phagocytosis and reduced synaptic markers (Synaptophysin, Psd-95).
- Wogonin treatment (100 mg/kg) significantly restored synaptic density and improved memory and cognitive deficits.
- Wogonin was found to inhibit microglial pro-inflammatory cytokine release and synaptic phagocytosis via AKT/FoxO1 pathway activation.
Conclusions:
- Wogonin effectively alleviates excessive synaptic pruning by microglia in epilepsy.
- Wogonin treatment improves cognitive dysfunction in epileptic mice through the AKT/FoxO1 pathway.
- Wogonin demonstrates potential as a therapeutic agent for epilepsy by modulating neuroinflammation and synaptic integrity.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.1K
01:03Long-term Depression
2.5K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
2.5K
01:14Antiepileptic Drugs: Glutamate Antagonists
284
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
284