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University of Calgary – Canada Brain Power

Canada Brain Power

Tag: University of Calgary

  • Identification of the Pannexin-1 channel in the brain as a target to treat opioid withdrawal symptoms

    Identification of the Pannexin-1 channel in the brain as a target to treat opioid withdrawal symptoms

    Brain Star Award feature: Erika Harding, Nicole Burma, Charlie Hong Ting Kwok, University of Calgary, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Opioids remain one of the most effective analgesics, with 10-15% of Canadians receiving opioid prescriptions per year. However, opioids are also highly associated with substance use disorders and overdose related deaths. Last year alone, over 7000 Canadians passed away from opioid overdose related complications. Many people who start with an opioid prescription enter a feedforward cycle of use reinforced by significant withdrawal symptoms. Patients report these symptoms as so aversive they will do anything to avoid them, and current treatments for opioid use disorder have a high degree of relapse. There is a clear need for better treatments of opioid withdrawal.

    Research done by Drs. Erika Harding, Charlie Hong Ting Kwok and Nicole Burma in the laboratory of Dr. Tuan Trang at the University of Calgary has identified a channel called Pannexin-1, present in a brain area called the Locus Coeruleus as a potential target to alleviate opioid withdrawal symptoms.

    Read the full story here: https://can-acn.org/brain-star-award-winners-erika-harding-charlie-kwok-and-nicole-burma/

    Read the original scientific publication:

    Kwok CHT*, Harding EK*, Burma NE*, Markovic T, Massaly N, van den Hoogen NJ, Stokes-Heck S, Gambeta E, Komarek K, Yoon HJ, Navis KE, McAllister BB, Canet-Pons J, Fan C, Dalgarno R, Gorobets E, Papatzimas JW, Zhang Z, Kohro Y, Anderson CL, Thompson RJ, Derksen DJ, Morón JA, Zamponi GW, Trang T. Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry. Nat Commun. 2024 Jul 24;15(1):6264. doi: 10.1038/s41467-024-50657-7. PMID: 39048565

    https://www.nature.com/articles/s41467-024-50657-7

  • Uncovering the role of cilia in astrocyte development and function

    Uncovering the role of cilia in astrocyte development and function

    Brain Star Award feature: Lizheng Wang, University of Calgary, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Astrocytes are a type of cells that act as crucial regulators of nearly all aspects of the brain. Different types of astrocytes exist; however, little is known about how different subtypes of astrocytes are created during development to differentially support their local neural circuits. Lizheng Wang, working in the laboratory of Jiami Guo at the University of Calgary, has discovered that a structure called the primary cilia acts as a small signaling antennae to transmit local cues and drive the region-specific diversification of astrocytes within the developing brain, and plays important roles in brain development.

    Discovered over 100 years ago, primary cilia are only beginning to be appreciated for their significance in the brain. Researchers have recently demonstrated that primary cilia of neurons are indispensable in regulating major neuronal development and functions, while the presence and function of cilia in astrocytes remained unexplored. This study shows that perturbation of astrocytic cilia leads to disruption of neuronal development and connections in the brain. Mice with primary ciliary deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory.

    Read the full story here

  • Mechanistic insights on how mice fed a high-fat diet have altered decision making could help define new therapeutical targets.

    Mechanistic insights on how mice fed a high-fat diet have altered decision making could help define new therapeutical targets.

    Diet-induced obesity is a major health concern because it is often associated with comorbidities including type 2 diabetes, stroke, cancer, and depression. Studies show that increased consumption of processed foods rich in sugar, fats, and salts can alter an individual’s ability to control their caloric intake, leading to overconsumption and higher body weight. New research led by Lauren Seabrook and Lindsay Naef at the University of Calgary provides insight to understand how obesogenic food alters neural circuits to bias behavior toward eating beyond satiety.

    For these discoveries, Lauren Seabrook and Lindsay Naef won a CAN-CIHR-INMHA Brain Star award.

    Using mice, the researchers investigated the effects of a high-fat diet on the lateral orbitofrontal cortex (lOFC) a key brain region that guides decision-making related to food intake, and made three exciting discoveries.

    First, they measured the activity of a subset of neurons called pyramidal neurons, and found they were more active in mice fed a high-fat diet.

    Second, they showed that the behaviour of obese mice was altered in ways that promote overeating. Normally a food reward can be devalued with satiety (feeling full) or by pairing the food with sickness (food poisoning). This devaluation was altered in obese mice, who continued feeding past satiety and in the presence of a taste that was paired to sickness.

    Third, the researchers were able to show that a specific neurotransmitter, GABA, acts to inhibit activity in the lOFC during food devaluation. Decreasing GABAaergic tone in lean mice promoted overeating behaviour, while increasing GABAergic tone in obese mice promoted food devaluation.

    Taken together, these findings provide new and exciting avenues to treat obesity by targeting the decision-making centers of the brain. Currently in Canada there are four medications used for the treatment of overweight and obesity, yet none of them specifically target brain mechanisms to alter food choices. These findings provide a novel target for potential therapeutics.

    This research was funded by a Koopmans Research Award, Mathison Centre for Research and Education Neural Circuits research grant, Canadian Institutes of Health Research operating grant (CIHR, FDN-147473) and a Canada Research Chair Tier 1 (950-232211) to Stephanie Borgland. Lauren Seabrook was supported by a Harley Hotchkiss Doctoral Scholarship in Neuroscience. Lindsay Naef was supported by postdoctoral awards from Les Fonds de la Recherche en Sante du Quebec, Alberta Innovates Health Solutions and CIHR.

    About Lauren T Seabrook & Lindsay Naef.

    Lauren T Seabrook and Lindsay Naef performed this research as a PhD student at the University of Calgary, in the laboratory of Dr. Stephanie Borgland. As co-first authors of the publication, she and Dr. Lindsay Naef performed most of the experiments, data analysis, and contributed significantly to the writing and editing of the manuscript. Dr. Naef currently works at Novo Nordisk.

    Scientific Publication

    Seabrook, L. T*., Naef, L*., Baimel, C., Judge, A. K., Kenney, T., Ellis, M., Tayyab, T., Armstrong, M., Qiao, M., Floresco, S. B., & Borgland, S. L. (2022). Disinhibition of the orbitofrontal cortex biases decision-making in obesity. * Co-first Nature neuroscience, 10.1038/s41593-022-01210-6. Dec 15 2022.

    https://doi.org/10.1038/s41593-022-01210-6