A. Microglia in neonatal development and neonatal ischemia
Dr. Eyo’s graduate research contributions were focused on elucidating the morphological dynamics of microglia in the early postnatal murine hippocampus. Using time lapse confocal microscopy, he investigated mechanisms guiding as well as documented microglial mobilization dynamics and mortality / survival especially under ischemic conditions which is abundant during the equivalent period in humans. Dr. Eyo also investigated the role of developmental apoptosis in regulating microglial mobilization and distribution properties during the early postnatal period and showed that apoptotic signals are not a predominant factor in regulating microglial entry / colonization of the hippocampus.
a. Eyo U, Dailey ME (2012) Effects of oxygen-glucose deprivation on microglial mobility and viability in developing mouse hippocampal tissues. Glia 60:1747-1760. (November, 2012 Journal Cover)
b. Eyo UB, Miner SA, Ahlers KE, Wu LJ, Dailey ME (2013). P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation.Neuropharmacology, 73C: 311-319.
c. Eyo UB, Miner SA, Weiner JA, Dailey ME (2016). Developmental changes in microglial mobilization are independent of apoptosis in the neonatal mouse hippocampus. Brain Behav. Immun., Jul; 55: 49-59.
B. Microglia in adult pathology: seizures, neuropathic pain and demyelination
Dr. Eyo has also been trying to understand microglial action in various pathologies of the mature CNS. His work has documented mechanisms guiding microglial-neuronal physical interactions in the mammalian brain where he specifically showed that excitatory neurotransmission especially through neuronal NMDA receptors as well as extracellular calcium depletion influence microglial dynamics via neuronal release of ATP. This is especially relevant during seizures. Furthermore, Dr. Eyo has contributed to findings that elucidate microglial mechanistic roles in demyelinating diseases and neuropathic pain as well as mechanisms of microglial activation following local neural tissue injury.
a. Eyo UB, Peng J, Przemyslaw S, Mukherjee A, Bispo A, Wu LJ (2014). Neuronal Hyperactivity Recruits Microglial Processes via Neuronal NMDA Receptors and Microglial P2Y12 Receptors after Status Epilepticus. Journal of Neuroscience, 34 (32): 10528-10540.
b. Eyo UB, Gu N, De S, Dong H, Richardson JR, Wu LJ (2015). Modulation of Microglial Process Convergence towards Neuronal Dendrites by Extracellular Calcium. Journal of Neuroscience, 35(6): 2417-2422.
c. Liu, J, Tian, D, Murugan, M, Eyo, UB, Dreyfus, CF, Wang, Wu, LJ (2015). Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage. Journal of Neurochemistry, 135(2): 347-356.
d. Swiatkowski P, Murugan M, Eyo UB, Wang Y, Rangaraju S, Oh SB, Wu, LJ (2016). Activation of microglial P2Y12 receptor is required for outward potassium currents in response to neuronal injury. Neuroscience, Mar 24 318:22-33.
e. Gu N, Eyo UB, Murugan M, Peng J, Matta S, Dong H, Wu LJ (2016). Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain Behav. Immun., Jul; 55: 82-92.
f. Peng J, Gu N, Zhou L, B Eyo U Murugan M, Gan WB, Wu LJ (2016). Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury. Nat Comm. 7:12029. doi: 10.1038/ncomms12029.
g. Gu N, Peng J, Murugan M, Wang X, Eyo UB, Sun D, Ren Y, DiCicco-Bloom E, Young W, Dong H,Wu LJ (2016). Spinal microgliosis due to resident microglial proliferation is required for pain hypersensitivity after peripheral nerve injury. Cell Reports. pii: S2211-1247(16)30758-6. doi: 10.1016/j.celrep.2016.06.018.
h. Eyo UB, Peng, J, Murugan M, Mo M, Lalani A, Xie P, Xu P, Margolis DJ, Wu LJ (2017). Regulation of Physical Microglia-Neuron Interactions by Fractalkine Signaling after Status Epilepticus. doi:10.1523/ENEURO.0209-16.2016.
i. Tian D, Peng J, Murugan M, Feng L, Liu J, Eyo UB, Zhou LJ, Mogilevsky R, Wang W, Wu LJ. 2017. Chemokine CCL2-CCR2 signaling induces neuronal cell death via STAT3 activation and IL-1β production after status epilepticus. Journal of Neuroscience, Aug 16;37(33):7878-7892. doi: 10.1523/JNEUROSCI.0315-17.
j. Eyo UB, Bispo A, Liu J, Sabu S, Wu Rong, DiBona VL, Zhang H, Tang Y, Wu LJ (2017). The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron Physical Interactions. Sci Rep, doi:10.1038/s41598-018-19205-4.
k. Eyo UB, Mo M, Yi M-H , Murugan M, Liu J, Yarlagadda R, Margolis DJ, Xu P, Wu LJ (2018). P2Y12R-Dependent Translocation Mechanisms Gate the Changing Microglial Landscape. Cell Rep. Apr 24; 23(4):979-966. doi: 1016/j.celrep.2018.04.001.
l. Bosco DB, Zheng J, Xu Z, Peng J,Eyo UB, Tang K, Yan C, Huang J, Feng L, Wu G, Richardson JR, Wang H, Wu LJ (2018). RNAseq analysis of hippocampal microglia after kainic acid-induced seizures. Mol Brain. 2018 Jun 20;11(1):34. doi: 10.1186/s13041-018-0376-5.
a. Eyo UB, Dailey ME (2013) Microglia: Key Elements in Neural Development, Plasticity and Pathology. Journal of Neuroimmune Pharmacology 8:494-509. DOI: 10.1007/s11481-013-9434-z (June, 2013 Journal Cover, Review).
b. Dailey ME, Eyo U, Fuller L, Hass J, and Kurpius D (2013) Imaging Microglia in Brain Slices and Slice Cultures. Cold Spring Harbor Protocols (December, 2013 Journal Cover, Review).
c. Eyo UB,Wu LJ (2013). Bi-directional microglia-neuron communication in the healthy brain. Neural Plasticity, 2013: 456857.
d. Eyo UB, Murugan M, Wu LJ (2017). Microglia-Neuron Communication in Epilepsy. Glia Jan;65(1):5-18. doi: 10.1002/glia.23006.
e. Zhao, X, Eyo UB, Murugan M, Wu LJ (2017). Microglial Interaction with the Neurovascular System in Physiology and Pathology. Neurobiol Jan 10. doi: 10.1002/dneu.22576.