I am an aging neuroscientist, interested in how we can prevent or repair the declines that occur during aging in learning and memory ability. I am hoping to figure this out before I forget what the question is.
We have been characterizing changes in the expression of a receptor that is very important for the formation of memories, the N-methyl-D-aspartate (NMDA) receptor. This receptor uses glutamate as a transmitter. The NMDA receptor shows greater declines in binding of glutamate with increased age than any of the other glutamate receptors, affecting both short- and long-term memory. Ultimately, we want to discover the mechanisms underlying the age-related changes in the NMDA receptor.
In order to enhance the translation of our work, we have recently developed a virtual water maze for testing human subjects. This task is designed to be similar to the water maze task that we use to assess memory in mice. We believe that this will enhance our ability to transition from screening interventions in mice to testing them in humans, by using the same task.
Recently, we have also begun to examine the role of that the gut microbiota and high energy diets play in cognitive abilities. We have found that animals fed a high sucrose diet show deficits in early learning and those fed either a high fat or high sucrose diet have trouble with cognitive flexibility. Certain alterations in the composition of the gut microbiota showed relationships to these cognitive problems. We are pursuing evidence of whether these deficits are due to diet alone or the microbiota.
Marquez-Loza AM, Elias V, Wong CP, Ho E, Bermudez M, Magnusson KR. (2017) Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging. Neuroscience 344:276-292.
McDougall M, Choi J, Magnusson KR, Truong L, Tanguay R, Traber MG. (2017) Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain metabolism due to redox-mediated mechanisms. Free Rad Biol Med 112:308-317.
Zhong JY, Magnusson KR, Swarts ME, Clendinen CA, Reynolds NC, Moffat SD. (2017) The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning. Behav Neurosci (in press).
Zamzow D, Elias V, Acosta V, Escobedo E, Magnusson KR. (2016) Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility. Age 38:50.
Magnusson KR, Hauck L, Jeffrey BM, Elias V, Humphrey A, Nath R, Perrone A, Bermudez LE. (2015) Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience 300:128-140.
Magnusson KR, Brim BL. (2015) The Aging Brain, Reference module in Biomedical Sciences, Michael Caplan (Editor-in-Chief), D.J. Holmes (Section Editor), Elsevier, Inc. 18-Oct-2014.
Zamzow DR, Elias V, Legette LL, Choi J, Stevens, JF, Magnusson KR. (2014) Xanthohumol improved cognitive flexibility in young mice. Behav Brain Res 275:1-10.
Zamzow DR, Elias V, Shumaker M, Larson C, Magnusson KR. (2013) An increase in the association of GluN2B containing NMDA receptors with membrane scaffolding proteins was related to memory declines during aging. J Neurosci 33:12300-12305.
Wong CP, Ho E, Magnusson, KR. (2013) Increased inflammatory response with age is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem 24:353-359.
Brim BL, Haskell R, Awedikian R, Ellinwood NM, Jin L, Kumar A, Foster TC, Magnusson KR. (2013) Memory in aged mice is rescued by enhanced expression of the GluN2B subunit of the NMDA receptor. Behav Brain Res 238:211-226.
Magnusson KR. (2012) Aging of the N-methyl-D-aspartate receptor - from a mouse's point of view. Future Neurol 7:627-637.
Das SR, Jensen R, Kelsay R, Shumaker M, Bochart R, Brim B, Zamzow D, Magnusson KR. (2012) Reducing expression of GluN1(0XX) subunit splice variants of the NMDA receptor interferes with spatial reference memory. Behav Brain Res 230:317-324.
Das SR, Magnusson KR. (2011) Changes in expression of splice cassettes of NMDA receptor GluN1 subunits within the frontal lobe and memory in mice during aging. Behav Brain Res 222:122-133.
Magnusson KR, Das SR, Kronemann D, Bartke A, Patrylo PR. (2011) The effects of aging and genotype on NMDA receptor expression in growth hormone receptor knockout (GHRKO) mice. J Gerontol A Biol Sci Med Sci 66:607-619.
Wong CP, Magnusson KR, Ho E. (2010) Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp Gerontol 45:163-169.
Magnusson KR, Brim BL, Das SR. (2010) Selective vulnerabilities of N-methyl-D-aspartate (NMDA) receptors during brain aging. Front Aging Neurosci 2:11.
Wong CP, Song Y, Elias VD, Magnusson KR, Ho E. (2009) Zinc supplementation increases zinc status and thymopoiesis in aged mice. J Nutr 139:1393-1397.