Mesenchymal stem cells improve sleep in anxious mice

A recent study explores the effects of mesenchymal stromal cells (MSCs) on sleep disorders in mice exhibiting anxiety. Approximately 50% of individuals with anxiety experience sleep disturbances, such as insomnia, which can worsen anxiety symptoms.

Current treatments for sleep disorders often include GABA sedative hypnotics and melatonin agonists. However, these medications can cause side effects like dizziness and fatigue, and they may not lead to satisfactory sleep quality. The goal of this research is to investigate whether MSCs can promote natural sleep and alleviate anxiety-like behaviors in mice.

To examine this, researchers created a mouse model of anxiety by genetically modifying C1 neurons to activate designer receptors. This was achieved by injecting AAV2-DIO-hSyn-hM3D(Gq)-mCherry into the rostral ventrolateral medulla (RVLM) of Dopamine-beta-Hydroxylase (DBH)-cre mice. The mice were then divided into two groups: the anxiety group (hM3D) and the treatment group receiving MSCs (hM3D+MSC). The study measured various sleep metrics using EEG and EMG to evaluate the effects of MSCs on sleep patterns.

Results showed that the latency to sleep increased and total sleep time decreased in anxious mice. However, after MSC infusion, sleep latency significantly decreased. Mice treated with MSCs transitioned more quickly from wakefulness to sleep, reducing awake time and increasing the duration of slow-wave sleep (SWS) and rapid eye movement sleep (REMS).

Further investigation into the brain regions affected by MSC treatment revealed activation in the ventrolateral preoptic area (VLPO) and lateral preoptic area (LPO), both critical for regulating sleep-wake transitions. Electrophysiological studies indicated that glutamatergic neurons in the VLPO responded notably to MSC treatment, while GABAergic neurons did not show a similar response.

This research suggests that MSCs can effectively shorten the time it takes for anxious mice to fall asleep and extend overall sleep duration by activating specific neurons in the VLPO. The findings highlight the potential of MSCs as a novel treatment avenue for sleep disorders associated with anxiety.