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Arc-Mediated Synaptic Plasticity Regulates Cognitive Function in a Migraine Mouse Model
Luyu Hu1, Qiaoyu Gong1, Yanjie Zhou1
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, No. 99, Zhangzhidong Road, Wuhan 430060, China.
Abstract:
Previous clinical and basic studies have shown that migraine is associated with cognitive impairment, anxiety, and depression. It severely affects the quality of life. In this study, C57BL/6 mice were randomly divided into four groups: IS group, IS+M group, and IS+S group with repeated application of dural inflammatory soup (IS) stimulation to establish a migraine model, followed by PBS, memantine, and sumatriptan interventions, respectively; the blank control group underwent the same treatment procedure but with PBS instead of IS and intervention drugs. The cognitive function of the mice was used as the main outcome indicator. After application of the IS, mice showed reduced pain threshold for mechanical stimulation, decreased learning memory capacity, attention deficit, a reduced number of dendritic spines in hippocampal neurons, and altered synaptic ultrastructure. The cognitive function indexes of mice in the IS+M group recovered with changes in Arc protein expression to a level not statistically different from that of the Control group, while the IS and IS+S groups remained at lower levels. The present results suggest that Arc-mediated synaptic plasticity may be an essential mechanism of cognitive dysfunction in migraine.
Insights
Migraine is linked to cognitive deficits. Memantine treatment in mice models improved learning and memory by restoring synaptic plasticity, suggesting a key mechanism for migraine-associated cognitive dysfunction.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Migraine is frequently associated with cognitive impairment, anxiety, and depression, significantly impacting patient quality of life.
- Basic and clinical studies indicate a strong link between migraine pathophysiology and neurological dysfunction.
Purpose of the Study:
- To investigate the impact of migraine induction on cognitive functions in a mouse model.
- To evaluate the therapeutic potential of memantine and sumatriptan on migraine-induced cognitive deficits.
- To explore the underlying mechanisms, specifically focusing on synaptic plasticity and Arc protein expression.
Main Methods:
- A migraine model was established in C57BL/6 mice using dural inflammatory soup (IS) stimulation.
- Mice were treated with phosphate-buffered saline (PBS), memantine (M), or sumatriptan (S).
- Cognitive function, pain threshold, hippocampal neuron dendritic spines, and synaptic ultrastructure were assessed. Arc protein levels were quantified.
Main Results:
- IS stimulation led to reduced pain threshold, impaired learning and memory, attention deficits, decreased dendritic spines, and altered synaptic ultrastructure.
- Memantine treatment significantly recovered cognitive function indexes to levels comparable to the control group.
- Arc protein expression changes correlated with cognitive recovery in the memantine group, unlike the sumatriptan group.
Conclusions:
- Arc-mediated synaptic plasticity is a critical mechanism underlying cognitive dysfunction in migraine.
- Memantine demonstrates potential in ameliorating migraine-associated cognitive impairments by targeting synaptic plasticity.
- Further research into synaptic mechanisms could reveal novel therapeutic targets for migraine-related cognitive issues.
