Effects of Microglia on Hippocampal Neurogenesis

• Applicant: Professor Dr. Frank Heppner
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243590644

• Final Report Year: 2020

Final Report Abstract

Adult neurogenesis plays a critical role in cognition and regeneration within the central nervous system (CNS). The presence of microglia, CNS resident myeloid cells, as neurogenic niche components has received little attention in the past. Our data within the frame of this DFG funded project demonstrate that hippocampal microglia serve a unique and indispensable physiological role in the maintenance of adult neurogenesis distinct from classical phagocytes or inflammatory cells. When microglia are lacking adult hippocampal neurogenesis is impaired which goes along with a severe deterioration of normal cognitive abilities. Upon replenishment of microglia in the hippocampus cognition is reversed identifying microglia as direct modulators and thus cellular targets of cognitive functions.

Publications

• High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol. 2016 Sep;132(3):361-75
  Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL
  (See online at https://doi.org/10.1007/s00401-016-1595-4)
• Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer's disease-like APPPS1 mice. Acta Neuropathol Commun. 2017 Jun 24;5(1):52
  Wagner LK, Gilling KE, Schormann E, Kloetzel PM, Heppner FL, Krüger E, Prokop S
  (See online at https://doi.org/10.1186/s40478-017-0453-5)
• (2018). CNS myeloid cells critically regulate heat hyperalgesia. J Clin Invest 128(7):2774-2786
  Kälin S, Miller KR, Kälin RE, Jendrach M, Witzel C, Heppner FL
  (See online at https://doi.org/10.1172/JCI95305)
• Intravenous injection of beta-amyloid seeds promotes cerebral amyloid angiopathy (CAA). Acta Neuropathol Commun. 2018 Mar 5;6(1):23
  Burwinkel M, Lutzenberger M, Heppner FL, Schulz-Schaeffer W, Baier M
  (See online at https://doi.org/10.1186/s40478-018-0511-7)
• (2019). Beclin1-driven autophagy modulates the inflammatory response of microglia via NLRP3. EMBO J. pii: e99430
  Houtman J, Freitag K, Gimber N, Schmoranzer J, Heppner FL, Jendrach M
  (See online at https://doi.org/10.15252/embj.201899430)