title: Minocycline rescues decrease in neurogenesis, increase in microglia cytokines and deficits in sensorimotor gating in an animal model of schizophrenia.
abstract: Adult neurogenesis in the hippocampus is impaired in schizophrenic patients and in an animal model of schizophrenia. Amongst a plethora of regulators, the immune system has been shown repeatedly to strongly modulate neurogenesis under physiological and pathological conditions. It is well accepted, that schizophrenic patients have an aberrant peripheral immune status, which is also reflected in the animal model. The microglia as the intrinsic immune competent cells of the brain have recently come into focus as possible therapeutic targets in schizophrenia. We here used a maternal immune stimulation rodent model of schizophrenia in which polyinosinic-polycytidilic acid (Poly I:C) was injected into pregnant rats to mimic an anti-viral immune response. We identified microglia IL-1β and TNF-α increase constituting the factors correlating best with decreases in net-neurogenesis and impairment in pre-pulse inhibition of a startle response in the Poly I:C model. Treatment with the antibiotic minocycline (3mg/kg/day) normalized microglial cytokine production in the hippocampus and rescued neurogenesis and behavior. We could also show that enhanced microglial TNF-α and IL-1β production in the hippocampus was accompanied by a decrease in the pro-proliferative TNFR2 receptor expression on neuronal progenitor cells, which could be attenuated by minocycline. These findings strongly support the idea to use anti-inflammatory drugs to target microglia activation as an adjunctive therapy in schizophrenic patients.
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany.
authors: Daniele
authors: D
authors: Mattei
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Charité Campus Mitte, 10117 Berlin, Germany.
authors: Anaïs
authors: A
authors: Djodari-Irani
authors: University Hospital, Clinic for Psychiatry and Psychotherapy, Experimental Psychiatry, 01307 Dresden, Germany.
authors: Ravit
authors: R
authors: Hadar
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany.
authors: Andreas
authors: A
authors: Pelz
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany.
authors: Lourdes Fernandez
authors: LF
authors: de Cossío
authors: University Hospital, Clinic for Psychiatry and Psychotherapy, Experimental Psychiatry, 01307 Dresden, Germany.
authors: Thomas
authors: T
authors: Goetz
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany.
authors: Marina
authors: M
authors: Matyash
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany.
authors: Helmut
authors: H
authors: Kettenmann
authors: University Hospital, Clinic for Psychiatry and Psychotherapy, Experimental Psychiatry, 01307 Dresden, Germany.
authors: Christine
authors: C
authors: Winter
authors: Max-Delbrück-Center of Molecular Medicine, Cellular Neuroscience, 13125 Berlin, Germany. Electronic address: susanne.wolf@mdc-berlin.de.
authors: Susanne A
authors: SA
authors: Wolf
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D008911:Minocycline / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects*; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D008911:Minocycline; D011070:Poly I-C
keywords: Animal model; Cytokines; Microglia; Minocycline; Neurogenesis; Neuroinflammation; Poly I:C; Schizophrenia; Sensorimotor gating