Neuroinflammation, Synaptic Plasticity and Cognitive Function
Susanna Rosi, PhD
Laboratory Mission Statement
Understand how neuroinflammation affect the molecular infrastructure mediating synaptic plasticity after brain injury to develop treatments strategies to manage neurocognitive dysfunctions.
Cognitive dysfunctions develop in response to a variety of insults to the CNS including disease or injury and constitute a significant factor with respect to overall function and quality of life. The pathogenesis of cognitive deficits is poorly understood and likely multifaceted. In particular, my lab is focused on elucidating how injury-induced alterations in neurogenesis, innate immune response, oxidative stress, post transcritpition/translational modifications, and chronic neuroinflammation affect various neural processes underlying cognitive function.
To examine the above effects, my laboratory employs three principle animal models: controlled cortical impact model of traumatic brain injury (TBI), therapeutic cranial γ-irradiation, and ionizing irradiation (HZE). Within these animal models we also examine multiple genotypes including CCR2rfp/+CX3CR1gfp/+, CCR2rfp/rfp,, CX3CR1gfp/gfp , TNFR1-/- mice, and McGill hAβPP rats. Our ultimate goal is to understand the mechanisms responsible for the cognitive dysfunction associated with neurodegenerative diseases, such as Alzheimer's disease, fronto-temporal dementia and other neurological-related disorders.
- Identify the dynamics of the post transcriptional infrastructure of gene expression involved in synaptic plasticity and memory after brain injury(traumatic brain injury, therapeutic irradiation and space irradiation)
- Determine the effects of brain injury (traumatic brain injury, therapeutic irradiation and space irradiation) on hippocampal network activity and function
- Determine how age at the time of injury affects hippocampal networks mediating contextual and spatial information processing
- Determine the role of the peripheral immune system in the evolution of cognitive deficits after brain injury
- Determine the role of oxidative stress and inflammation on synaptic functions after exposure to space radiation
Funding and Contributors
National Institute of Aging (NIA)
National Cancer Institute (NCI)
National Aeronautics and Space Administration (NASA)
Antino Allen, PhD, University of Arkansas Medical School, Little Rock, AR
Carol A Barnes, PhD, University of Arizona, Tucson, AZ
Michael Beattie, PhD, University of California San Francisco, San Francisco, CA
Jacqueline Bresnahan, PhD, University of California San Francisco, CA
Claudio Cuello, MD, McGill University, QC, Canada
Adam Ferguson, PhD, University of California San Francisco, CA
Nigel Greg, PhD, National Institute of Health, Bethesda, MD
Nalin Gupta: MD, PhD, University of California San Francisco, CA
Charlie Limoli, PhD, University of California Irvine, Irvine, CA
Ting-Ting Huang, PhD Stanford University, CA
Geoffrey Manley, MD, PhD, University of California San Francisco, CA
Gregory Nelson, PhD, Loma Linda University, Loma Linda, CA
Jacob Raber, PhD, Oregon Health Science University, Portland, OR
Victor Ramirez-Amaya, PhD, Universidad Nacional Autonoma de Mexico, Mexico
Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF, Barnes CA, Wenk GL. Neuroinflammation alters the pattern of behaviorally induced Arc in the hippocampus (2005) Journal of Neuroscience. 25(3): 723-731.
Ramirez-Amaya V, Vazdarjanova A, Mikael D, Rosi S, Worley PF, Barnes CA. Coordinate Arc mRNA and protein expression in the neuronal networks activated by spatial exploration (2005) Journal of Neuroscience. 25(7): 1761-1768.
Rosi S, Andres-Mach M, Fishman K, Ferguson R, Levy W, Fike JR. Cranial irradiation alters the behaviorally-induced immediate early gene Arc (activity-regulated cytoskeleton-associated protein) (2008) Cancer Research, Dec 1; 68 (23):9763-70. [PMCID: PMC2597278]
Rosi S, Ramirez-Amaya V, Vazdarjanova A, Esperanza EE, Larkin P, Fike JR, Wenk GL, Barnes CA. Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine (2009) Brain; 132:2464-77. [PMCID: PMC2732266]
Belarbi K, Arellano C, Ferguson R, Jopson T, Rosi S. Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Brain Behav Immun. 2012 Jan;26(1):18-23. Epub 2011 Jul 20.
Rosi S, Ferguson R, Fishman K, Raber J, Fike RJ. The polyamine inhibitor α-Difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries. PlosOne 2012;7(1):e31094. Epub 2012 Jan 27.
Belarbi K, Jopson T, Tweedie D, Arellano C, Luo W, Greig NH, Rosi S. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J of Neuroinflammation. 2012 Jan 25;9:23.
Belarbi K, Jopson T, Arellano C, Rosi S. CCR2 deficiency prevents neuronal dysfunction and cognitive impairments induced by cranial irradiation.
Cancer Research, 2013 Feb 1;73(3):1201-10. Epub 2012 Dec 13.
Ramirez-Amaya V, Argulo P, Chawla M, Barnes C, Rosi S. Sustained transcription of the immediate early gene Arc in the dentate gyrus after spatial exploration. Journal of Neuroscience, 2013 Jan 23;33(4):1631-1639.