Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats.
Microglia, the innate immune cells of the central nervous system, regulate brain development by promoting cell genesis, pruning synapses, and removing dying, newly-born or progenitor cells. However, the role of microglia in the early life programming of behavior under normal conditions is not well characterized. We used central infusion of liposomal clodronate to selectively deplete microglia from the neonatal rat brain and subsequently assessed the impact of microglial depletion on programming of juvenile and adult motivated behaviors. Liposomal clodronate treatment on postnatal days one and four led to greater than 70% loss of forebrain microglia by postnatal day 6 that lasted for approximately ten days. Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior on the elevated plus maze and open field test, and increased locomotor activity. On a test of juvenile social play, microglial depletion led to decreased chase behaviors relative to control animals. There was no change in active social behavior in adults on a reciprocal social interaction test, but there was decreased passive interaction time and an increased number of social avoidance behaviors in clodronate treated rats relative to controls. There was an overall decrease in behavioral despair on the forced swim test in adult rats treated neonatally with clodronate. Females, but not males, treated neonatally with clodronate showed a blunted corticosterone response after acute stress in adulthood. These results show that microglia are important for the early life programming of juvenile and adult motivated behavior.
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, USA; Group in Behavioral Neuroendocrinology, The Ohio State University, Columbus OH, USA. Electronic address: nelson.1246@osu.edu.
Lars H
LH
Nelson
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave., Columbus, OH 43210, USA; Department of Psychology, The Ohio State University, 1835 Neil Ave., Columbus, OH 43210, USA; Group in Behavioral Neuroendocrinology, The Ohio State University, Columbus OH, USA. Electronic address: lenz.56@osu.edu.
Kathryn M
KM
Lenz
D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002135:Calcium-Binding Proteins; D004002:Clodronic Acid / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012919:Social Behavior; D013550:Swimming / Q000523:psychology
C100745:Aif1 protein, rat; D050071:Bone Density Conservation Agents; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D004002:Clodronic Acid