Chronic Neuroinflammation, Learning and Memory

Principal Investigator

Laboratory Mission Statement

Our studies are aimed to understand how neuroinflammation contributes to the cognitive dysfunction associated with Alzheimer's disease, traumatic brain injury, therapeutic brain irradiation and other neuroinflammatory-related disorders. Understanding the molecular alterations that contribute to neuroinflammation-related cognitive impairment one of the most important goals for prevention and treatment.

General overview

The ability of our brain to form and store new memories involves modulation of the strength and efficacy of synaptic signaling and is mediated by de novo synthesis of genes and proteins. Dysfunction of hippocampal synaptic plasticity results in loss of memory functions and is a characteristic of many neurodegenerative diseases such as Alzheimer’s disease. Dysfunction of hippocampal synaptic plasticity can be also a long term consequence of traumatic brain injury, therapeutic brain irradiation or normal ageing. Although neuronal dysfunction is the ultimate consequence of these disorders, alteration in the microenvironment in which the neurons live, by activation of the innate immune system, seems to be the key factor for the progression of these memory related disorders.

In my laboratory we use in vivo animal models of lipopolysaccharide-induced neuroinflammation, cranial irradiation, traumatic brain injury or combined injury to study how chronic neuroinflammation disrupts activity patterns associated with synaptic plasticity, learning and memory consolidation.

Areas of focus

Neuroinflammation
Plasticity-related immediate early gene Arc (activity regulated cytoskeleton-associated protein)
Neuron-microglia comunication
Role of Tumor Necrosis Factor-(TNF-α) on learning and memory
Brain Irradiation and altered synaptic plasticity and memory
Long term effects of traumatic brain injury and cognition
Hippocampal network stability
Functional integration of adult born neurons into behaviorally-relevant networks
Information processing in the hippocampus (input and output in the entorhinal cortex-dentate-hippocampal system).

Funding and Contributors

NIH, NCI, Alzheimer’s Association

Laboratory members

Collaborators

Carol A Barnes, Ph.D. Professor, Departments of Psychology and Neurology; Evelyn F. McKnight Chair for Learning and Memory in Aging, University of Arizona, Tucson, AZ.

Paula Bickford, PhD gt;. Professor, Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL.

Nigel Greig, PhD. Senior Investigator, National Institute of Health, Drug Design and Development Section, Laboratory of Neurosciences, NIA
Gerontology Research Center, Baltimore, MD.

Charlie Limoli, Ph.D. Professor, Department of Radiation Oncology, University of California Irvine, Irvine, CA.

Jacob Raber, Ph.D. Professor, Department of Behavioral Neuroscience, Oregon Health Science University, Portland, OR.

Victor Ramirez Amaya, PhD. Associate Professor, Instituto de Neurobiologia, Univercidad Nacional Autonoma de Mexico, Queretaro, Mexico.

David Tweedie, PhD. Investigator, National Institute of Health, Drug Design and Development Section, Laboratory of Neurosciences, NIA
Gerontology Research Center, Baltimore, MD.

Selected Publications

Rosi S. (2011) Neuroinflammation and the plasticity-related immediate-early gene Arc. Brain Behavior and Immunity. [Epub ahead of print; doi: 10.1016/j.bbi.2011.02.003], [NIHMS273755].

Rosi S, Belarbi K, Ferguson RA, Fishman K, Obenaus A, Raber J, Fike JR. (2010) Trauma Induced Alterations in Cognition and Expression of the Behaviorally-Induced Immediate Early Gene Arc are Reduced by a Previous Exposure to 56Fe. Hippocampus. [Epub ahead of print; DOI: 10.1002/hipo.20920].

Rosi S, Ramirez-Amaya V, Vazdarjanova A, Esperanza EE, Larkin P, Fike JR, Wenk GL, Barnes CA. (2009) Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine. Brain. (132)2464-77.

Rosi S, Andres-Mach M, Fishman K, Ferguson R, Levy W, Fike JR. (2008) Cranial irradiation alters the behaviorally-induced immediate early gene Arc (activity-regulated cytoskeleton-associated protein). Cancer Research. 68(23):9763-70.

Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF, Barnes CA, Wenk GL. (2005) Neuroinflammation alters the pattern of behaviorally induced Arc in the hippocampus. Journal of Neuroscience. 25(3): 723-731.

Rosi S, Vazdarjanova A, Ramirez-Amaya V, Worley PF, Barnes CA, Wenk GL. (2006) Memantine reduces the consequences of chronic neuroinflammation and restores the hippocampal pattern of behaviorally-induced Arc expression. Neuroscience. 142(4):1303-15.

Rosi S, Pert CB, McGann-Gramling and Wenk GL. (2005) CCR5 Chemokine Receptor Antagonist regulates microglia and astrocytes activation within the hippocampus in a neuroinflammatory rat model of Alzheimer's disease. Neuroscience. 134 (2):671-6.

Rosi S, Ramirez-Amaya V, Hauss-Wegrzyniak B, Wenk GL. (2004) Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors. Journal of Neuroinflammation. 1(1):12-18.

Rosi S, Giovannini MG, Lastage PJ, Munoz C, Pepeu G. (2004) S-18986-1, a positive modulator of AMPA receptors with cognition-enhancing properties, increases Ach release in the hippocampus of young and aged rat. Neuroscience Letters. 361: 120-3.