RT Journal Article
SR Electronic
T1 Selective Ablation of BDNF from Microglia Reveals Novel Roles in Self-Renewal and Hippocampal Neurogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4172
OP 4186
DO 10.1523/JNEUROSCI.2539-20.2021
VO 41
IS 19
A1 Harley, Samuel B. R.
A1 Willis, Emily F.
A1 Shaikh, Samreen N.
A1 Blackmore, Daniel G.
A1 Sah, Pankaj
A1 Ruitenberg, Marc J.
A1 Bartlett, Perry F.
A1 Vukovic, Jana
YR 2021
UL http://www.jneurosci.org/content/41/19/4172.abstract
AB Microglia, the resident immune cells of the CNS, have emerged as key regulators of neural precursor cell activity in the adult brain. However, the microglia-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 pathologic 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.