Abstract
Microglia, the resident immune cells of the CNS, have emerged as key regulators of neural precursor cell activity in the adult brain. However, the microglial-derived factors that mediate these effects remain largely unknown. In the present study, we investigated a role for microglial brain-derived neurotrophic factor (BDNF), a neurotrophic factor with well-known effects on neuronal survival and plasticity. Surprisingly, we found that selective genetic ablation of BDNF from microglia increased the production of newborn neurons under both physiological and inflammatory conditions (e.g. LPS-induced infection and traumatic brain injury). Genetic ablation of BDNF from microglia otherwise also interfered with self-renewal/proliferation, reducing their overall density. In conclusion, we identify microglial BDNF as an important factor regulating microglia population dynamics and states, which in turn influences neurogenesis under both homeostatic and pathological conditions.
SIGNIFICANCE STATEMENT
(1) Microglial BDNF contributes to self-renewal and density of microglia in the brain. (2) Selective ablation of BDNF in microglia stimulates neural precursor proliferation. (3) Loss of microglial BDNF augments working memory following traumatic brain injury. (4) Benefits of repopulating microglia on brain injury are not mediated via microglial BDNF.
Footnotes
The authors declare no competing interests.
J.V. holds a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Foundation and also acknowledges support from both the Australian Research Council (Discovery Early Career Research Award 150101578) and National Health and Medical Research Council (NHMRC; Project Grant 1124503). S.B.R.H was supported by an Australian government Research Training scholarship, a Queensland Brain Institute student top-up scholarship and a UQ career development scholarship extension. E.F.W. was supported by the University of Queensland Senate Scholarship Herdsman Fellowship in Medical Science and a UQ career development scholarship extension. M.J.R was supported by SpinalCure Australia, the Wings for Life Spinal Cord Research Foundation, and the NHMRC (1060538 and 1163835). We thank Robert Sullivan for experimental assistance. We thank the staff of The University of Queensland’s Biological Resources Facility for breeding and maintaining the animals in this study. Imaging was performed at the Queensland Brain Institute's Advanced Microscopy Facilities using Yokogawa and Diskovery spinning disk confocal microscopes, Imaris software, and the stereology microscope, supported by the Australian Government through the ARC LIEF grant LE100100074. Behavioral tests were performed at the Queensland Brain Institute's Behavior and Surgical Facility. The authors also acknowledge the facilities, and the scientific and technical assistance of the National Imaging Facility at the Centre for Advanced Imaging, University of Queensland.
Member Log In
Log in using your username and password
Purchase access
