Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M.
Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood.
Nat Neurosci. 2006 Feb;9(2):268-75.
Please login to recommend the paper.
To make a comment you must login or register.
This paper supports the general theory of bidirectional and tight communication between the nervous and immune systems. Microglia as components of both organ systems are critical players, presumably translating the T cell presence into a phenotype associated with increased cell proliferation and improved memory. Potential mediators include microglial IGF-1, and neuronally derived BDNF. The use of immune-deficient mouse models, both SCID and nude, coupled with the T cell adoptive transfer experiments and the T/MBP transgenic mouse provides in my mind pretty compelling evidence that brain-directed T cells facilitate neurogenesis and also improve hippocampal function as tested by a standard hippocampal-dependent behavioral task.
This study is also significant because it raises some interesting possibilities for neurodegenerative disorders in addition to the role of the immune system in maintaining "normal" brain function.
One intriguing question is whether the brain, during enrichment, expresses signaling or trophic molecules that induce the trafficking of brain-specific T cells into distinct regions of the brain. Is there something different about microglia (and other resident cells) within the brains of these immune-deficient mice that reduces the expression of molecules involved in both basal and enrichment-induced neurogenesis?
It is tempting to speculate on the ramifications of these results for Alzheimer disease, particularly in view of the interest in vaccines and antibody strategies targeting β amyloid. Are there endogenous T cells circulating in those of us without AD that continuously survey the brain, help maintain neuronal health (and neurogenesis), as well as inducing microglia to mop up amyloid fibrils and microdeposits before they reach plaque status? Moreover, what is the relationship between the cellular and humoral arms of the immune system with respect to both neurogenesis, cognition, and Alzheimer disease? Like any good science, this study opens up the field to more questions than answers.