Mice Research Sheds Light on Role of Anxiety in Insomnia

For many being anxious, stressed, or even being too excited can cause sleepless nights. Although emotions are recognized to affect wakefulness and even cause insomnia, the underlying mechanisms for why this occurs has been unclear.

Now, from an animal study, Japanese researchers believe they have discovered a neurochemical root cause on how emotions can trigger insomnia. Scientists believe the finding could led to future discovery of drug targets for anxiety disorder and/or sleep disorders.

Investigators explain that biological responses occur when we evolutionarily encountered predators, or as we adapt to a novel environment or expect a reward.

These stressful or emotionally salient situations require individuals to shift their behavior to a vigilant state, altering their physiological conditions through modulation of autonomic and endocrine functions. This response begins in a part of the brain called the amygdala, specifically in the nucleus of the nerve nexus called the stria terminalis (BNST). The amygdala is generally considered a key player in stress response, fear, and anxiety.

The BNST controls endocrine and autonomic reactions in response to emotionally-salient stimuli along with behavioral expression of anxiety and fear. The region does this by sending projections to various brain regions including relay nuclei of the autonomic nervous system, hypothalamic regions and the central nucleus of the amygdala.

Dr. Takeshi Sakurai, vice director of the International Institute for Integrative Sleep Medicine, and his team found that acute optogenetic excitation of GABAergic neurons in BNST during non-rapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state.

The stimulation did this without the function of orexins, highly important neuropeptides for maintaining wakefulness. Notably, stimulation of the same neurons during REM sleep did not show any effects on sleep/wakefulness states.

Prolonged excitation of GABAergic neurons in BNST evoked a longer-lasting, sustained wakefulness state, and it was abolished by administering a receptor blocker in advance, meaning that orexins are involved in this phenomenon.

“Our study revealed a role of the BNST GABAergic system in sleep/wakefulness control, especially in shifting animals’ behavioral states from NREM sleep to wakefulness.

“It also provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation, which will hopefully lead to the first step to develop remedies for sleep disorders,” Sakurai said.

Source: University of Tsukuba