How to Fires Up our Synapses

Processing of sensory impressions and information depends very much on how the synapses in our brain work. A team around chemist Robert Ahrends from the University of Vienna and neuroscientist Michael R. Kreutz from Leibniz Institute for Neurobiology in Magdeburg now showed how lipid and protein regulation impact brain’s processing of a beautiful and stimulating environment. The lipids located in the membranes of the synapses are central to signal transmission, the researchers report in “Cell Reports“.

“We usually enjoy a beautiful environment, socializing, a cosy apartment, good restaurants, a park – all this inspires us,” says Robert Ahrends from the Institute of Analytical Chemistry of the University of Vienna and former group leader at ISAS in Dortmund. Previous studies have already shown that such an enriched environment can sometimes have a positive effect on child development or even on the human ability to regenerate, e.g. after a stroke, however the reason for these observations “was not yet clarified at the molecular level“.

Stimulating sensory perceptions are ultimately formed via the activity or regulation of synapses, i.e. those connecting units between our neurons that transfer information from one nerve cell to another. To clarify the underlying molecular principles, the researchers offered the rodents, their model organisms, an enriched environment based on plenty of room to move, a running wheel and other toys.

With the help of post-genomic analysis strategies (multiomics) and using state-of-the-art mass spectrometry and microscopy as well as bioinformatics for data analysis, they investigated the regulation of synapses in the hippocampus of the rodents, more precisely the interaction of the proteins and especially lipids (fats) located in the synaptic membranes.

80 percent of the brain cells are only supporting cells. We have therefore focused on the synapses as central sites of signal transmission and isolated them,” says neuroscientist Michael Kreutz. The team gathered quantitative and qualitative information about the network of molecules regulated at synapses and examined their lipid metabolism, also under the influence of an enriched environment.
The analyses revealed that 178 proteins and 20 lipids were significantly regulated depending on whether the rodents had spent time in an enriched environment or an uncomfortable one.


How To Boost Brain’s Synapses

A team of researchers at Stanford University has found synapse-boosting factors in the blood of young mice. In their paper published in Proceedings of the National Academy of Sciences, the group describes their study of the rejuvenating impact of blood from young mice when transfused into older mice, and what they learned about it.

Prior research has shown that transfusing blood from young (12 to 15 months old) into older mice can reverse some of the signs of aging in the brain and sometimes other parts of the body—a process called parabiosis. While researchers have studied the effect, it is still not clear which factors in young blood provide the rejuvenating effects. In this new effort, the researchers looked deeper into the phenomenon and found two possible answers.

To learn more about parabiosis in mice, the researchers transfused serum from mice between the ages of 12 and 15 months into older mice to study its impact. They also did the same with 15-day-old mice. In so doing, they found that the youngest mouse blood resulted in more pronounced neuronal dendrite branching, a bigger increase in the number of , and a bigger increase in the release of neurotransmitters compared to blood from less . They also found that it provided more improvements in N-methyl-D-aspartate receptor-mediated synaptic function in the older mice. They next found that applying the to neurons cultured in the lab did the same. And finally, they found that doing so also boosted synaptic connectivity. Conversely, they found that applying serum from older mice to younger mouse neurons had the opposite effect.

To isolate the properties in the young serum that were behind the rejuvenating effect, the team looked at samples using tandem —they isolated two proteins (thrombospondin-4 and SPARC-like protein-1) that appeared richer in the younger serum. When the two proteins were applied to the older , some of the same rejuvenating effects took place, suggesting that they were at least two of the factors responsible for the rejuvenating effect. The researchers suggest that the blood of young mice likely holds many kinds of synapse-promoting factors that decline as mice age.