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Glia and Glia-Neuron Interaction

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

STAT3 pathway in microglia is involved in cognitive function

  • P3-020
  • Jeong-Kyu Han:1 Sun-Ho Kwon:2 
  • 1:Department of Brain & Cognitive Sciences, Seoul National University, Seoul, Korea 2:Department of Pharmacology, College of Medicine, Seoul National University 

Microglia are recently emerged as key players for synaptic plasticity in normal brain development and adult physiology. In particular, they actively do synaptic remodeling by regulating structure and function. Although recent studies show that microglia itself have crucial roles, however, specific mechanisms still remain unclear. To make concrete, we used microglia specific STAT3 knock-out (KO) mice via Cre-Lox recombination system. First of all, we performed a variety of behavior tests. Forced swimming tests showed that behavioral motility was increased in STAT3 KO group. This implicates that JAK2/STAT3 signal pathway in microglia might have influence on neuronal function of emotion. To confine this behavior result, we used electrophysiological approach in order to investigate synaptic activity changes. In parallel fiber-purkinje cell (PF-PC) synapse, miniature excitatory postsynaptic current (mEPSC) was measured through whole cell patch recording to identify whether it came from presynaptic or postsynaptic. Statistically, cumulative probability of inter-event interval (IEI) showed that synaptic events were more frequently occurred in STAT3-deficient mice. However, amplitude of events had no difference between control and knock-out groups. This suggests that there must be presynaptic modulators from microglia, which is related to STAT3 pathway. Downward to molecular level, we found the level of S100A9, calcium binding modulator, was increased in STAT3-deficient mice via RT-PCR. In addition, paired-pulse ratio (PPR) was increased when STAT3 was absent in microglia, presuming the relationship between spontaneous and evoked release. In terms of synaptic remodeling, microglial migration might be one of the possible mechanisms related to STAT3 protein. We set up the live cell imaging system, testing knock-down (KD) of STAT3 in BV2 microglial cell line, then found the cellular velocity of STAT3 KD group was decreased. This implies that synaptic contact by microglia have influence on synaptic reconstruction. In conclusion, it makes possible to expand our understanding of the cognitive function based on synapse-microglia interaction from microglia STAT3-deficient mice model.

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