14 DAY TRIAL // If you have just forgotten what you ate in the morning or whom you have met, you should put the blame on proteins. Scientists say short-term memories are made of modifying proteins, while long-term memories are built by new proteins. Thus, chemicals impeding brain cells from processing proteins could inhibit the formation of new memories, inducing amnesia.
But a new research challenges this long term concept and could lead to the development of new therapies for Alzheimer and other conditions that induce dementia and memory loss. While investigating the biochemical action induced by the protein synthesis inhibitor anisomycin in the amygdala (the center of the emotional memories), the team at the University of Illinois at Urbana-Champaign noted something unusual in the midbrain area.
The amounts of three neurotransmitters (norepinephrine, dopamine and serotonin) boomed up from 1,000 to 17,000 % over their normal levels before dropping to well below normal for eight to 48 hours.
"We know that anisomycin causes the large release of neurotransmitters. Those neurotransmitters themselves regulate memory formation and that's the basis of the particular phenomenon," said senior author Paul Gold, a professor in the university's Brain and Cognition Division.
Gold's team started the investigation on lab rats to see if neurotransmitter fluctuation modulated memory formation. The researchers placed animals in a cage with one well-lit and one darkened compartment. Each time rats entered the dark side, they would get a shock to their feet. 48 hours later, they hesitated to enter that compartment.
The researchers injected anisomycin and propranolol, a chemical that stops norepinephrine receptors in the brain, into the rats' amygdalae.
"We [essentially] blocked the biological consequences of the release of norepinephrine," said Gold.
This minimized the rats' memory loss, revealed by their reluctance to enter the shock-inducing dark zone of the chamber. The amnesia induced by anisomycin was also less powerful when they injected the animals with clenbuterol, a chemical that boosts norepinephrine release, when their neurotransmitter levels were low. When a high amount of norepinephrine was administered instead of anisomycin, before training, the extra neurotransmitter quantities induced amnesia (just like anisomycin).
"Together, these findings suggest that intra-amygdala injections of anisomycin interfere with memory formation by inducing extraordinary changes in the release profiles of [norepinephrine, dopamine and serotonin]." wrote the researchers. Future investigations will establish if all protein synthesis inhibitors induce the same effect on neurotransmitters and in other brain areas, too.
"Protein synthesis has been known to modulate neurotransmitter levels since the 1960s. The link between novel protein production and memory formation has been observed in several neural circuits in organisms ranging from mollusks to mammals," said Yadin Dudai, a neurobiologist at the Weizmann Institute of Science in Rehovot, Israel.
"If the neurotransmitter fluctuation-based view does demote the dogma, there could be implications for researchers searching for drugs to counteract the effects of dementia that occur in diseases such as Alzheimer's." said Gold. The new targets will be rather neurotransmitters than proteins.