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The last thing anyone wants to remember is trauma. It can haunt you with flashbacks, nightmares, night terrors, and overwhelming fears you never thought you would have.
In The Invisible Man, an already traumatized Cecilia struggles with being literally haunted by ghosts that nobody else believes exist. Unfortunately, traumatic events don’t just exist in sci-fi horror movies. There are too many horrific things you can go through that can be horribly scarring. You would obviously rather forget whatever experience it was that traumatized you, but how exactly does the human brain ward off those memories and the fears they breed?
Neuroscientists from the Tokyo University of Sciences, who recently published a study in Behavioral Neuroscience, think they have found the answer for erasing, instead of facing, memories that switch on fear. This is known as fear extinction. Your brain synthesizes a compound known as KNT-127 that activates delta-opioid receptors which are associated with mood. While the scientists were aware it was behind fear extinction from a previous study, what exactly activates it had been a mystery until now.
"We have found that KNT-127 activates δ-opioid receptors and downstream signaling pathways in brain regions, which are known to be essential to achieve fear extinction," Yamada told SYFY WIRE.
Losing control in itself can be terrifying. The inability to control memories of trauma that trigger fear is thought to be an underlying cause of PTSD, panic disorder, and other anxiety disorders. SSRIs and benzodiazepines are often used to treat these conditions. SSRIs (serotonin reuptake inhibitors) increase the levels of the neurotransmitter serotonin, one of the many chemical messages fired by neurons in the brain, by preventing it from being re-absorbed into neurons. Benzodiazepines affect the neurotransmitter GABA (gamma-aminobutyric acid) in a way that slows the nervous system down for a sedative effect that reduces anxiety or panic.
Unfortunately, some patients are unresponsive to either type of medication, and both have side effects. Benzodiazepines in particular are potentially addictive. Neither SSRIs or benzodiazepines directly extinguish fear, either. An alternative treatment that targets KNT-127 could be more effective and avoid the risk for addiction. The research team put mice through living nightmares, and with fear conditioning, the mice soon realized that a certain stimulus to the brain would result in being zapped in the foot with electric shock.
"The PI3K/Akt and MEK/ERK signaling pathways are common cellular mechanisms of gene expression also in the memory processes," Yamada said. "Although we did not approach its downstream target molecules, activating these pathways may facilitate extinction memory consolidation."
When the mice were shocked, they froze. That was their fear response. Different parts of their brains were injected with KNT-127 before they went through fear conditioning again. The regions of the brain found to be responsive were basolateral nucleus of the amygdala (BLA) and the infralimbic subregions (IL). The BLA is believed to control learning after a stressful experience, while the IL is involved in threat responses, and the neurotransmitters released during such a response can possibly explain why your blood pressure rises when you’re sweating in fear.
Freezing reactions were much less severe with a boost of KNT-127. It could also be reversed. There are certain signaling pathways — the chemical reactions that molecules in a cell use to control that cell’s function — that inhibit KNT-127. When the mice were injected with these, the therapeutic effects from before were cancelled out and relief turned back into fear. The KNT-127 injections actually had the same effect as diazepam, the benzodiazepine otherwise known as Valium. Cecilia is on this medication in The Invisible Man.
This study could have huge implications for the treatment of trauma and anxiety. Though there have been no trials on humans yet, and scientists are going to have to figure out how to develop a treatment that is not a massive injection to the brain, Yamada thinks KNT-127 is much more inclusive than SSRIs or benzos that may set off wildly different reactions in different individuals (if there is a reaction at all).
"Fear extinction is considered to be the biological basis of exposure therapy for the treatment of PTSD and anxiety disorders," he said. "Our findings will provide useful and important information for the development of evidence-based therapeutics."
Someday, we will no longer be haunted by the specter of trauma.