Poster Presentation The International Congress of Neuroendocrinology 2014

Endocannabinoid-induced phagocytosis in the developing amygdala mediates a sex difference in cell genesis (#196)

Jonathan W VanRyzin 1 , Margaret M McCarthy 2
  1. Program in Neuroscience, University of Maryland, Baltimore, Baltimore, MD, United States
  2. Departments of Pharmacology and Physiology, University of Maryland, Baltimore, Baltimore, Maryland, United States

The mechanisms underlying the establishment of sex differences in the developing brain are still largely unknown, but recent evidence suggests an increasing role for non-neuronal cells in this process.  Microglia aid in synaptic pruning, tissue homeostasis, and regulate neuronal precursor populations through signaling and targeted phagocytosis of viable cells- termed “phagoptosis”.  To further support this, we implicated microglia as an integral component of brain sexual differentiation in the preoptic area1, suggesting an important signaling capacity of these cells in organizing sex-specific brain structure and behavior.  Additionally, we reported a sex difference in cell proliferation in the developing rat medial amygdala (MeA) that was mediated by endocannabinoids, with females having higher cell proliferation rates than males.  These differences in cell proliferation correlated to behavioral changes, as female treatment with the CB1/2 agonist WIN55,212-2 masculinized juvenile social play behavior2.  Further investigation revealed a surprising new role for microglia in mediating the number of newborn cells with effects specific to the postnatal MeA.  Males displayed twice as many Iba1+ microglia exhibiting a phagocytic morphology as compared to females.  These microglia contained one or more processes that ended in a phagocytic cup, but otherwise exhibited thick or ramified processes.  Furthermore, exogenous CB1 receptor agonist treatment increased the number of phagocytic microglia in females to levels observed in males.  Treatment with the tetracycline derivative minocycline, an inhibitor of microglial activation, increased male BrdU+ cell counts to female levels, but did not alter the number of female BrdU+ cells.  We found every microglia exhibiting a phagocytic morphology was also DAPI+, a marker for DNA, within the phagocytic cup; thus, we sought to characterize the specific cell types targeted by the microglia.  BrdU colocalized to the phagocytic cup, in addition to inhibitory interneuron markers calbindin and nNos.  This work was supported by RO1 MH52716-018 to MMM.

  1. K.M. Lenz, B.M. Nugent, R. Haliyur, & M.M. McCarthy (2013) Microglia are essential to masculinization of brain and behavior. J. Neurosci. 33(7):2761-2772
  2. D.L. Krebs-Kraft, M.N. Hill, C.J. Hillard, & M.M. McCarthy (2010) Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior. PNAS 107(47):20535-20540