Dr. Angela Scott

Neural communication and the intricate choreography of signals required for the formation and preservation of neural function is heavily dependent on the interactions between neurons and glial cells (myelinating cells, astrocytes, microglia). While neurons provide the essential wiring within the nervous system, glial cells are responsible for a myriad of functions that determine the quality, maintenance, and re-growth of these connections. Given the cellular diversity of the nervous system, uncovering the roles of glial cells is integral to understanding basic neurobiological function and the pathology of many neurological disorders.

In the lab, we take an integrative and comparative approach to study glial-neuronal interactions in relation to early development, physical injury, and neurological disease that spans across multiple levels of biological organization (molecular and cellular physiology > systems biology) and multiple model species (zebrafish and mice).

B.Sc. (Hons) Physiology, University of Saskatchewan

B.A. (Distinction) Psychology, University of Saskatchewan

Ph.D. Neuroscience, University of British Columbia

Postdoctoral Fellow, Centre for Neuroregeneration at the University of Edinburgh

Postdoctoral Fellow, Department of Biology, McMaster University

Postdoctoral Fellow, Department of Pathology and Molecular Medicine, McMaster University

My research aims to understand the dynamic molecular and cellular relationships that underlie neurological dysfunction during developmental or regenerative processes within the central nervous system. I am particularly interested by the intercellular interactions between neuronal and non-neuronal (glial) cells, and how these interactions govern adaptive and maladaptive plasticity as the system develops, ages, or is inflicted by trauma or disease. My research program can be divided into two general areas: 1) investigation of glial-mediated mechanisms underlying development and disease and; 2) exploration of naturally adaptive models with significant recovery from, or tolerance to, neurological stress or disease.

1) Astrocytes are intimately associated with neurons at sites of newly forming and mature synapses (tripartite synapse), and the interactions between these cell types are integral to regulating development (growth, migration, synapse formation) and maintaining homeostatic functions (ion balance, excitability, survival). In particular, we focus on astrocytic regulation of purine and pyrimidine signalling, and the physiological consequences related to changes in the gliotransmission in Fragile X Syndrome (FXS). Notably, perturbations in ATP/UTP signalling significantly impacts glial physiology and highly contributes to the abnormal neural circuitry associated with FXS, the leading genetic cause of Intellectual Disability and Autism Spectrum Disorders. We are exploring these novel cellular and molecular relationships in FXS and in astrocyte-mediated regulation of brain development, including neurogenesis, synaptogenesis, metabolic homeostasis and oxidative stress.

2. We are also applying these approaches to the study of stress responses within the CNS. We are interested in the adaptive strategies of stress-tolerant animal models and natural ‘regenerators’. The use of zebrafish as a model species provides a great opportunity to study highly adaptive forms of neuroplasticity, particularly those involved in neuroprotection and regeneration. Ongoing work has found interesting differences in purinergic signalling, evolutionary conserved in fish, using established protocols to examine radial glial interactions that underlie injury-induced CNS neurogenesis in zebrafish.

Pan, W., Godoy, R., Cook, D., Scott, A., Nurse, C. and Jonz, M. (2022) Single-cell transcriptomic analysis of chemosensory neuroepithelial cells and other cell trypes of the gills of zebrafish (Danio Rerio) exposed to normoxia and hypoxia. Scientific Reports 12 (11): 10144 (17 pages).

Stefanova, E. and Scott, A. (2022) Purinergic signaling systems across comparative models of spinal cord injury. Neural Regeneration Research 17 (11): 2391-98.

Vandenberg, G., Thotakura, A., and Scott, A. (2022) Mitochondrial bioenergetics of astrocytes in Fragile X Syndrome: new perspectives on culture conditions and sex effects. American Journal of Physiology – Cell Physiology 322: C125-135.

Reynolds, K., Krasovska, V. and Scott, A. (2021) Converging purinergic and immune signaling drive IL-6 secretion by Fragile X cortical astrocytes. Journal of Neuroimmunology 361: 577745.

Reynolds, K., Wong, C., and Scott, A. (2021) Dysregulation of purinergic signalling underlies astrocyte-mediated alterations to synaptogenesis during development in Fragile X Syndrome. GLIA 69 (7): 1816-1832.

Vandenberg, G., Dawson, N., Head, A., Scott, G. and Scott, A. (2021) Astrocyte-derived metabolic stress present in the developing Fragile X Syndrome cortex. Neurochemistry International 146: 105036.

Pan, W., Scott, A., Nurse, C., and Jonz, M. (2021) Identification of oxygen-sensitive neuroepithelial cells through an endogenous reporter. Cell and Tissue Research 384 (1): 35-47.

Scott, A., Pranckevicious, N., Nurse, C. and Scott, G. (2019) Adaptations to hypoxia-induced stress responses in high-altitude deer mice. American Journal of Physiology - Integrative Comparative Physiology 317 (3): R407-17.

Nurse, C., Salman, S., and Scott, A. (2018) Hypoxia-regulated catecholamine secretion in chromaffin cells. Cell and Tissue Research, 372 (2): 433-441.

Wallingford, J., Scott, A., Rodrigues, K. and Doering, L. (2017) Altered developmental expression of the astroctye-secreted factors Hevin and SPARC in the Fragile X mouse model. Frontiers in Molecular Neuroscience 10; article 268: 1-12. doi:10.3389/fnmol.2017.00268.

Barreiro-Iglesias, A.*, Mysiak, K.*, Scott, A.*, Reimer, M., Becker, C., and Becker, T. (2015) Serotonin promotes regeneration of motor neurons, but not serotonergic interneurons in the spinal cord of adult zebrafish. Cell Reports 13 (5): 924-932. 2015. *co-first author

Scott, A., Zhang, M. and Nurse, C. (2015) Enhanced BDNF signalling following chronic hypoxia potentiates catecholamine release from adrenal chromaffin cells. Journal of Physiology 593 (15): 3281-3299.

Reimer, M., Norris, A., Ohnmacht, J., Patani, R., Zhong, Z., Dias, T., Kuscha, V., Scott, A., Chen, Y., Rozov, S., Frazer, S., Wyatt, C., Higashijima, S., Patton, E., Panuala, P., Chandran, S., Becker, T., and Becker, C. (2013) Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration. Developmental Cell 25 (5): 478-91.

Scott, G., Schulte, P., Egginton, S., Scott, A., Richards, J., Milsom, W. (2011) Molecular evolution of cytochrome c oxidase underlies high-altitude adaptation in the bar-headed goose. Molecular Biology and Evolution 28 (1): 351-63.

Scott, A., and Ramer, M. (2010) Schwann cell p75NTR prevents spontaneous sensory re-innervation of the adult spinal cord. Brain 133 (2): 421-432.

Cragg, J., Scott, A., and Ramer, M. (2010) Depletion of spinal 5-HT promotes mechanosensory recovery in the deafferented spinal cord. Experimental Neurology 222 (2): 277-284.

Scott, A., and Ramer, M. (2010) Differential regulation of dendritic plasticity by neurotrophins following deafferentation of the adult spinal cord is independent of p75NTR. Brain Research 1323: 48-58.

Ramer, M., Cruz Cabrera M., Alan, N., Scott, A., and Inskip, J. (2010) A new organelles complex in rat sympathetic neurons. PLoS One 5 (5): e1000872.

Scott, A.*, Ramer, L.*, Soril, L., Kwiecien, J., and Ramer, M. (2006) Targeting myelin to optimize plasticity of spared axons in the denervated spinal cord. Molecular Neurobiology 33 (2): 91-111. *co-first author

Scott, A., Borisoff, J., and Ramer, M. (2005) Deafferentation and neurotrophic-mediated intraspinal sprouting: a central role for the p75 neurotrophic receptor. European Journal of Neuroscience 21 (1): 81-92.

Graduate students

Alexandra Law

Matt Napier (PhD)

Isaac Sullivan (MSc)

Eva Stefanova (previous MSc, lab technician)

Syeda Kashaf Gilani

Undergraduate students

Natasha Szulist (4th year thesis)

Cinthiya Sugumar (4th year thesis)

Sidney Kang (4th year thesis)

Matin Borhani (3rd year project)

Danielle Zak (3rd year project)

Previous lab members

Graduate Students

Kathryn Reynolds (PhD)

Gregory Vandenberg (MSc)

Undergraduate students

Caitlin Atkinson (2nd, 3rd + 4th year, summer student)

Amira Benaini (4th year)

Jasleen Jagayat (4th year)

Shirley Andrews (2nd + 3rd year)

Olivia Kalau (4th year)

Eliza Wiseman (4th year)

Aysan Nexamabadi (3rd year)

Amanda Poxon (3rd + 4th year, summer student)

Vivian Wong (3rd year)

Hazra Chowdry (4th year)

Ahmed Shoeib (3rd year, summer student)

Aasritha Thotaka (3rd and 4th year)

Stephanie Scott (3rd year)

Jia Zhong (4th year)

Joshua Ling (4th year)

Katarina Iacobucci (2nd + 4th year)

Alison Head (4th year)

Danielle Harris (3rd year)

Julian Dychiao (3rd + 4th year)

Jazlynn Sandhu (4th year)

Eileen Huang (4th year)

David Shin (3rd year, summer student)

Chloe Wong (3rd + 4th year, summer student)

Monica Sabbineni (USRA summer student)