- Scientists have observed genes responsible for helping mice recover from strokes.
- This could provide guidance for humans.
- Drugs could be developed to target these specific genes.
<p>Scientists at Stanford Medicine recently observed that some mice recovered from strokes better than others, leading them to wonder whether or not they could find evidence that specific genes played a role in recovery. They did.</p><p>The results of the study — which can be read <a href="https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.021508" target="_blank">here</a> — describes thirty-three male mice with strokes and seven mice without strokes being charged with balancing on a "horizontal rotating beam" — running out across and back. After the stroke, the mice couldn't do this. Two weeks after the stroke, 25% of the mice were able to recover well enough to run across the length of the beam and back. </p><p>Previous research into stroke recovery in mice has noted that sensory deprivation has pushed its brain in a more healthy direction <a href="https://medicine.wustl.edu/news/stroke-recovery-improved-sensory-deprivation-mouse-study-shows/" target="_blank">if its whiskers were trimmed</a>; <a href="http://stm.sciencemag.org/content/10/441/eaao6459" target="_blank">blocking an immune response aids stroke recovery</a>; <a href="https://med.stanford.edu/news/all-news/2015/12/stroke-recovery-in-mice-improved-by-ambien-study-shows.html" target="_blank">Ambien can aid in recovery</a>; there's research that talks about a rich, playful environment aiding in a mouse's recovery, which is featured in the video below; and even <a href="https://www.lerner.ccf.org/news/details/?Grape+Powder+Improves+Stroke+Recovery+in+Mice&a66de3c2800832c85f64c0c75490da96db53f805&59cf824c7c50298a497694fa945ad7d15f0fd3fd" target="_blank">a grape-rich diet can help improve stroke recovery in mice</a>.<br><br>Why look at <em>genetic</em> recovery in mice? "Understanding the genes regulated post-stroke could help us design novel ways to treat patients in the days and weeks after the initial event," <a href="https://journals.lww.com/neurotodayonline/Fulltext/2018/10040/At_the_Bench_Stroke_Recovery__Researchers_Uncover.9.aspx" target="_blank">Michelle Y. Cheng is quoted as saying</a>. <br><br>What was found? "Distinct biological pathways" in the portion of the motor cortex opposite the lesion wrought by the stroke as well as pathways on the same side of lesion-affected cortex. There were 38 genes on the side of the brain impacted by the lesion associated with recovery and 74 genes opposite the lesion that were associated with recovery.<br></p>
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="14c4f66888e459443aa6d255d39c7d56"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/0PSrRIEhgBc?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>A majority of these genes are involved with something called cAMP signaling. cAMP signaling detects molecules outside already existing cells and has a role in determining a response.</p><p>'cAMP signalling' activates a protein called a protein kinase that modifies other proteins in the body that send signals off somewhere else. Broadly speaking, cAMP signalling also has a role in memory, water absorbed in the kidney, whether or not the heart is relaxed, breaking down fats, and more.</p><p>The particular genes involved in cAMP signalling that played a role in stroke recovery for the mice are called <a href="https://en.wikipedia.org/wiki/Adenosine_A2A_receptor" target="_blank">adenosine receptor A2A</a>, <a href="https://en.wikipedia.org/wiki/Dopamine_receptor_D2" target="_blank">dopamine receptor D2</a>, and <a href="https://en.wikipedia.org/wiki/PDE10A" target="_blank">phosphodiesterase 10A</a>. Receptors are protein molecules embedded in cell membranes that respond to external stimuli to transmit information somewhere else. The A2A is often a target of caffeine. It is a protein that is abundant in platelets, lymphocytes, and more. The D2 receptor is typically the target of most antipsychotic drugs. Current research suggests that there might be a link between phosphodiesterase 10A and obesity. <br><br>In the case of post-stroke recovery, however, the study notes that activating A2A "signaling within a few hours poststroke can reduce inflammatory cell infiltration after stroke"; that "activation of Drd2 on astrocytes in acute stroke can reduce neuroinflammation"; and that "inhibition of Pde10a may be a promising therapeutic strategy for psychiatric and neurodegenerative diseases."<br><br>There are complications — blocking A2A signaling can help against a lesion-induced toxicity; and not only does Drd2 inhibit cAMP communicating with the rest of the body, but "the role of Drd2 in brain repair is also unclear." </p><p>Nevertheless, this is research that makes the figurative target of our interest a little clearer and a little sharper, illustrating where medicine can take aim next.</p>
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