Gene Expression Shifts as Shrews Shrink and Regrow Their Brains

As winter approaches, people within the greater latitudes would possibly beat the chilly by snuggling up beneath a pile of blankets or reserving a timeshare in sunny Florida. Equally, some animals address seasonal adjustments by slowing their metabolisms to a crawl to drop into hibernation or endeavor lengthy migrations to extra hospitable climes.

However Sorex araneus, often known as the frequent shrew, doesn’t appear to have the ability to put the brakes on its terribly quick metabolism—it has one of many highest basal metabolic charges of any mammal—and its diminutive stature makes long-distance migrations extremely impractical.¹ As an alternative, the shrew advanced a considerably peculiar technique: it shrinks. 

Scientists have noticed reductions not simply in general physique mass, but additionally within the dimension of the shrews’ livers, spleens, skulls, and brains.^2,3 Researchers hypothesize that lowering the mass of metabolically-costly tissues helps the shrews preserve power, permitting them to outlive on much less meals throughout the winter months when their prey—bugs, slugs, and worms—is harder to return by. 

This loss isn’t with out penalties—their shrunken brains are much less able to spatial studying.⁴ Happily for the shrews, additionally it is reversible: After dropping 20 % of their mind mass within the fall, they regain about 10 % the next spring, going by means of this course of simply as soon as throughout their roughly year-long lifespans.³ Now, a global workforce of researchers has characterised variations in gene expression within the mind, each over time and between species, that might clarify the shrew’s outstanding plasticity in mind and physique mass, which is called Dehnel’s phenomenon.⁵ They printed their findings yesterday (November 19) as a reviewed preprint in eLife.

“It’s totally thrilling,” stated Liliana Dávalos, an evolutionary biologist at Stony Brook College, who coauthored the research together with Dina Dechmann, a behavioral ecologist on the Max Planck Institute of Animal Habits, and John Nieland, a neuroscientist at Aalborg College. “There’s quite a lot of potential for understanding the mechanics of mind reorganization in an organism that naturally shrinks and regrows, which is one thing that [humans] can’t do. We’re simply on a one-way journey in the direction of shrinking and degenerating.”

In earlier work, the analysis workforce examined transcripts within the shrews’ cortex and hippocampus—mind areas which can be essential for studying and reminiscence—however within the current research, they shifted their focus to the hypothalamus.⁶ “The hypothalamus is a relay heart within the mind to take care of metabolic homeostasis,” defined William Thomas, a postdoctoral fellow within the Dávalos analysis group and coauthor of the research. “However we’re additionally trying on the hypothalamus as a result of it’s a area that shrinks and regrows as nicely.” Thus, the hypothalamus might present insights into the metabolic signaling underlying the total-body restructuring in addition to the scale adjustments inside the mind itself.

The researchers began by analyzing gene expression in shrews throughout totally different factors within the lifecycle, together with in autumn (when the shrews’ brains had been shrinking) and in spring (when their brains had been regrowing). In comparison with autumn shrews, spring shrews displayed upregulation of transcripts that code for parts of inhibitory synapses and downregulation of a number of genes within the apoptosis pathway.  Whereas the implications of those variations stay to be decided, the findings prompt that synaptic plasticity within the hypothalamus could also be associated to Dehnel’s phenomenon. Moreover, the authors speculated that pro- and anti-apoptotic components might assist the shrew management each cell loss of life and cell proliferation throughout this course of.

Dávalos and her workforce additionally in contrast the spring shrew gene expression profiles with publicly obtainable information from species in a number of different mammalian orders, trying to find genes or pathways that gave the impression to be uniquely up- or down-regulated in S. araneus. In comparison with different mammals, two pathways had been considerably enriched within the shrew hypothalamus: Certainly one of these concerned genes associated to intracellular signalling and the second included genes liable for recycling proteins and different parts inside the cell. Lastly, the researchers in contrast the outcomes of the seasonal and cross-species analyses to determine particular person genes that had been in a different way expressed in each information units. 5 genes match the profile, together with CCDC22, which can play a task within the regulation of inflammatory signaling, and FAM57B, which regulates synaptic construction.^7,8

Whereas this research recognized many intriguing variations throughout species, Thomas famous that there are some limitations to the conclusions that may be drawn from the sort of comparability. Since there have been no publicly obtainable hypothalamic RNA datasets for different species of shrew, the researchers weren’t capable of evaluate S. araneus to its kinfolk. “So, we don’t know if all shrews expertise this up-regulation or if it is truly associated to Dehnel’s phenomenon,” he famous. “It might simply be some type of up-regulation that is related to having excessive metabolisms or simply being a shrew on the whole.”

Moreover, since hypothalamic gene expression responds to environmental change, it might be troublesome to tease aside the extent to which variations in gene expression are advanced diversifications or responses to an animal’s present atmosphere. However, a complete characterization of gene expression over time in a species that shows such outstanding mind plasticity remains to be worthwhile. 

“What I like about this strategy—utilizing RNA [sequencing]—is that it’s type of a broad stroke strategy,” stated Christine Schwartz, a hibernation biologist on the College of Wisconsin-La Crosse who was not concerned within the research. In species about which comparatively little is thought, stated Schwartz, investigating a single candidate gene won’t flip up something. “However, if you happen to’re capable of examine many [genes] at a time over the course of related time factors… then you definitely’re capable of see these large adjustments in teams of genes—or perhaps genes that you just would not have even considered is likely to be concerned. In order that’s actually beneficial from a scientific perspective.” 

Dávalos stated that that is solely simply starting; this research lays the groundwork for future explorations into gene features and drivers of Dehnel’s phenomenon. She additionally famous that it’s nonetheless unknown whether or not these drivers of mind shrinkage and regrowth will probably be relevant to human neurodegenerative illness.

“On one hand, we predict that the shrew as a system is tremendous thrilling as a result of it is giving us insights into the boundaries of what a mammal can do,” stated Dávalos. “However, we have now to respect the truth that it is a shrew, and we’re not going to search out some form of magic bullet. That is merely not how biology works.”

Whereas their work offers the muse for mechanistic research that might someday inform methods to advertise mind regeneration in people, Dávalos stated, “We’re additionally very passionate concerning the shrew, for the shrew’s sake.”