Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. 2013 Dec 19;155(7):1596-609. PubMed.
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Third Rock Ventures
This paper reports a groundbreaking piece of work. The major new conceptual insight is that microglia play critical roles (as do all brain cells) in the development and maintenance of the CNS. One can no longer think of “resting” microglia because they’re never at rest, any more than one speaks of “resting” and “activated” neurons. From this point forward, one must consider that altered microglial physiology (as during systemic infection, neurodegeneration, trauma, stroke, immune-mediated inflammation) may entail loss of physiological function (such as BDNF production, as in this paper, or IGF1 [Ueno et al., 2013]) possibly in addition to gain of toxic function, culminating in CNS dysfunction. One only has to think of the recent publication from Frank Heppner's lab (Krabbe et al., 2013) describing microglial impairment in a murine AD model to begin to imagine the many research questions emerging from the present publication, in context with other reports from this year alone. On a technical level the mice described here, in combination with a different model recently published (Goldmann et al., 2013), will enable unprecedented manipulation of microglia in genetic models. Finally there is a plethora of fascinating questions coming from this paper. How does the specific requirement for microglial BDNF, for example, relate to microglial-neuronal communication? Why does loss of microglial BDNF affect some but not other learning tasks?
References:
Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, Yamashita T. Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci. 2013 May;16(5):543-51. Epub 2013 Mar 24 PubMed.
Krabbe G, Halle A, Matyash V, Rinnenthal JL, Eom GD, Bernhardt U, Miller KR, Prokop S, Kettenmann H, Heppner FL. Functional impairment of microglia coincides with Beta-amyloid deposition in mice with Alzheimer-like pathology. PLoS One. 2013;8(4):e60921. PubMed.
Goldmann T, Wieghofer P, Müller PF, Wolf Y, Varol D, Yona S, Brendecke SM, Kierdorf K, Staszewski O, Datta M, Luedde T, Heikenwalder M, Jung S, Prinz M. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci. 2013 Nov;16(11):1618-26. Epub 2013 Sep 29 PubMed.
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