As a shrew’s brain shrinks and regrows, gene expression changes

no wayAs winter approaches, humans in higher latitudes can beat the cold by cuddling up under a pile of blankets or booking a timeshare in sunny Florida. Likewise, some animals cope with seasonal changes by slowing their metabolism, going into hibernation, or moving for extended periods of time to more hospitable climates.

but Taurus (Sorex araneus)Also known as shrews, they can’t seem to put the brakes on their incredibly fast metabolism. Highest basal metabolic rate The mammal’s proportions and small stature make long-distance migration very impractical.¹ Instead, shrews have developed a rather unique strategy. In other words, your body becomes smaller.

Scientists observed a decrease in the size of the shrews as well as their overall weight. liverspleen, skull and brains.^2,3 Researchers hypothesize that reducing the amount of metabolically expensive tissue will help shrews conserve energy, allowing them to survive on less food during the winter months when prey (worms, slugs, and worms) are more difficult to obtain.

These losses are not without consequences. Their shrunken brains become less capable. spatial learning.⁴ Fortunately, this phenomenon is reversible. After losing 20% ​​of our brain volume in the fall, we regain about 10% the following spring. This process is performed only once, over a period of approximately one year.³ Now, an international research team has characterized the following differences: gene expression This may explain the remarkable plasticity in brain and body mass of shrews, a phenomenon that appears in the brain over time and across species, known as the Dehnel phenomenon.⁵ They published their findings in a reviewed preprint yesterday (November 19). e-life.

“It’s very interesting,” he said. Liliana DavalosAn evolutionary biologist at Stony Brook University, he co-authored the study. Dina DeckmanBehavioral ecologist at the Max Planck Institute for Animal Behavior John Niland, Neuroscientist at Aalborg University. “There is a lot of potential to understand the mechanisms of brain reorganization in organisms that naturally shrink and regrow. [humans] I can’t. “We are just on a one-sided journey that leads to atrophy and degeneration.”

In a previous study, the research team examined the transcripts of tomboys. cortex and hippocampus—a brain region important for learning and memory—but the current study shifted focus to the hypothalamus.⁶ “The hypothalamus is the brain’s relay center that maintains metabolic homeostasis.” william thomasis a postdoctoral researcher in Dávalos’ research group and a co-author of the study. “But we are also focusing on the hypothalamus because it is an area that can shrink and grow again.” The hypothalamus can therefore provide insight into the metabolic signals that underlie changes in the size of the brain itself, as well as overall restructuring of the body.

The researchers started by analyzing the shrews’ gene expression at various points in their life cycle, including fall (when their brains shrink) and spring (when their brains regrow). Compared to autumn shrews, spring shrews displayed upregulation of transcripts encoding components of inhibitory synapses and downregulation of several genes in the apoptotic pathway. Although the meaning of these differences has not yet been determined, our findings suggest that synaptic plasticity in the hypothalamus may be related to Denel’s phenomenon. Moreover, the authors speculated that pro- and anti-apoptotic factors may help shrews regulate both apoptosis and cell proliferation during this process.

Dávalos and her team also compared spring shrew gene expression profiles with publicly available data from species from several other mammalian orders, searching for genes or pathways that appeared to be uniquely up- or down-regulated. S. Araneus. Compared to other mammals, two pathways were significantly enriched in the shrew hypothalamus. One of these was associated with genes involved in intracellular signaling, and the second involved genes that recycle proteins and other components within cells. Finally, the researchers compared the results of the seasonal and cross-species analyzes to identify individual genes that were differentially expressed in the two data sets. Five genes fit the profile, including: CCDC22, can play a regulatory role inflammation signaland FAM57Bregulating synapse structure.^7,8

Although the study identified many interesting differences across species, Thomas noted that there are some limitations to the conclusions that can be drawn from this type of comparison. Because there were no publicly available hypothalamic RNA datasets for other species of shrews, the researchers were unable to make comparisons. S. Araneus To relatives. “So we don’t know whether all shrews experience this upregulation, or whether it is actually related to the Dehnel phenomenon,” he said. “It could just be the kind of upregulation associated with having a high metabolism or being a tomboy in general.”

Moreover, because hypothalamic gene expression responds to environmental changes, it can be difficult to isolate the extent to which differences in gene expression have evolved as adaptations or responses to the animal’s current environment. Nonetheless, it is still valuable to comprehensively characterize gene expression over time in a species that displays such remarkable brain plasticity.

“What I like about this approach is the use of RNA. [sequencing]—That it’s kind of a broad approach,” he said. Christine SchwarzA hibernation biologist at the University of Wisconsin-La Crosse was not involved in the study. In species where relatively little is known, examining a single candidate gene may yield nothing, says Schwartz. “But if we could research a lot of things. [genes] Across all relevant points at once… Then you can see these big changes in groups of genes. Or maybe there’s a gene involved that you didn’t even think about. So this is really valuable from a scientific perspective.”

Dávalos said this is just the beginning. This study lays the foundation for future exploration of gene function and drivers of Dehnel phenomenon. She also noted that it is not yet known whether these factors of brain shrinkage and regrowth can be applied to neurodegenerative diseases in humans.

“On the one hand, I think shrews are very interesting as a system because they provide insight into the limits of what mammals are capable of,” Dávalos said. “On the other hand, we have to respect the fact that this is a tomboy, and we’re not going to find some kind of magic bullet. This is simply not how biology works.”

While their work provides the basis for mechanistic studies that could one day inform strategies to promote human brain regeneration, Dávalos said, “We’re also very passionate about shrews.”