Microglia provide structural resolution to injured dendrites after severe seizures
Ukpong B. Eyo,
Koichiro Haruwaka,
Mingshu Mo,
Antony Brayan Campos-Salazar,
Lingxiao Wang,
Xenophon S. Speros, IV,
Sruchika Sabu,
Pingyi Xu,
Long-Jun Wu
Affiliations
Ukpong B. Eyo
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Brain Immunology and Glia Center, Department of Cell Biology and Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Corresponding author
Koichiro Haruwaka
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Mingshu Mo
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangdong 510120, China
Antony Brayan Campos-Salazar
Brain Immunology and Glia Center, Department of Cell Biology and Neuroscience, University of Virginia, Charlottesville, VA 22908, USA
Lingxiao Wang
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
Xenophon S. Speros, IV
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
Sruchika Sabu
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
Pingyi Xu
Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangdong 510120, China
Long-Jun Wu
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA; Corresponding author
Summary: Although an imbalance between neuronal excitation and inhibition underlies seizures, clinical approaches that target these mechanisms are insufficient in containing seizures in patients with epilepsy, raising the need for alternative approaches. Brain-resident microglia contribute to the development and stability of neuronal structure and functional networks that are perturbed during seizures. However, the extent of microglial contributions in response to seizures in vivo remain to be elucidated. Using two-photon in vivo imaging to visualize microglial dynamics, we show that severe seizures induce formation of microglial process pouches that target but rarely engulf beaded neuronal dendrites. Microglial process pouches are stable for hours, although they often shrink in size. We further find that microglial process pouches are associated with a better structural resolution of beaded dendrites. These findings provide evidence for the structural resolution of injured dendrites by microglia as a form of neuroprotection.