Acute Stress May Block a Key Anxiety-Relieving Neuropeptide
Stress-induced anxiety may impair neuropeptide Y's ability to calm the brain.
Posted Jan 04, 2017
Neuropeptide Y (NPY) is a self-produced molecule in the brain that has robust anxiety-relieving effects. New research on mice suggests that acute stress blocks the endogenous production of NPY and triggers a neurobiological chain reaction that may cause anxiety to snowball out of control. The findings by researchers at the UAB department of neurobiology led by Lynn Dobrunz were published today in The Journal of Neuroscience.
Previous studies have found that Neuropeptide Y triggers several reactions in the body and brain that include anxiety and stress reduction, lowering blood pressure, increasing pain tolerance, and making people less inclined to consume too much alcohol.
As a neuropeptide, NPY directly influences the hippocampus, which is a brain area considered to be the hub of learning and memory. Notably, studies on people with post-traumatic stress disorder (PTSD) and other anxiety disorders found that they tend to have less self-produced neuropeptide Y in their brains.
The latest NPY mouse study identified a chain reaction in which stress-induced anxiety impairs the self-production of NPY. Various levels of NPY appear to drive circuit functions of a specific region of the hippocampus called "CA1" which is linked to the formation of aversive fear-based memories. The combination of low NPY and modulated CA1 synaptic function seems to make it easier for the brain to hardwire any stimuli associated with something scary into long-term memory.
Neuropeptide Y Modulates Synaptic Plasticity of the CA1 Hippocampal Region
In laboratory mice, exposure to a scent associated with a predator triggers stress-induced anxiety which impairs the endogenous production of neuropeptide Y. Lower levels of NPY make the long-term memory hub of the hippocampus in a mouse more susceptible to imprinting fear-based memories associated with the scent of a dangerous predator.
Once a fear-based memory is imprinted, exposure to any stimuli associated with this traumatic memory can trigger stress-induced anxiety. This phenomenon appears to drive a vicious cycle of less and less NPY production along with more and more imprinting of aversive memories in the hippocampus. Eventually, this cycle can lead to paralyzing fear-evoked freezing and debilitating avoidance behaviors.
While reading about the latest research on neuropeptide Y, I was reminded of combat veterans who have harrowing flashbacks of being in a war zone that can be triggered by seemingly innocuous stimuli they encounter in daily life.
For example, in a 60 Minutes report, “The War Within: Treating PTSD,” a veteran named Gable Darbonne describes how the smell of diesel from any roadside gas station in his hometown sends him right back to being in a combat zone overseas. The smell of diesel gasoline opens a floodgate in his mind to a tidal wave of fear-based memories. This association prompted Darbonne to avoid filling his tank at the gas station—which caused him to drive less and less. Eventually, this avoidance behavior led him to become a somewhat agoraphobic shut-in.
Future Research on Neuropeptide Y Could Lead to New Treatments for PTSD
The good news is that the groundbreaking research on NPY being conducted at UAB offers a potential new target for treating PTSD and other anxiety disorders. In the abstract of their latest study, the UAB researchers conclude,
“Our results demonstrate how stress alters CA1 circuit function through the impairment of endogenous NPY release, potentially contributing to heightened anxiety.
By demonstrating that NPY release modulates hippocampal synaptic plasticity and is impaired by predator scent stress, our results provide a novel mechanism by which stress-induced anxiety alters circuit function.”
The new research on the link between stress, neuropeptide Y, and the CA1 region of the hippocampus fills an important gap in previous knowledge about the molecular and behavioral effects of NPY.
The researchers are optimistic that their ongoing research could pave the way for new therapeutic targets to increase endogenous NPY release in patients who suffer from PTSD, anxiety disorders or panic attacks. Stay tuned!
Endogenously Released Neuropeptide Y Suppresses Hippocampal Short-Term Facilitation and Is Impaired by Stress-Induced Anxiety. Qin Li, Aundrea F. Bartley, Lynn E. Dobrunz. Journal of Neuroscience 4 January 2017, 37 (1) 23-37; DOI: 10.1523/JNEUROSCI.2599-16.2017