Early Life Exposure to Tumor Necrosis Factor Induces Precocious Sensorimotor Reflexes Acquisition and Increases Locomotor Activity During Mouse Postnatal Development

Abstract

Inflammation appears as a cardinal mediator of the deleterious effect of early life stress exposure on neurodevelopment. More generally, immune activation during the perinatal period, and most importantly elevations of pro-inflammatory cytokines levels could contribute to psychopathology and neurological deficits later in life. Cytokines are also required for normal brain function in homeostatic conditions and play a role in neurodevelopmental processes. Despite these latter studies, whether pro-inflammatory cytokines such as Tumor Necrosis Factor (TNF) impact neurodevelopmental trajectories and behavior during the immediate postnatal period remains to be elucidated. To address this issue, we have injected mouse pups daily with recombinant TNF from postnatal day (P)1 to P5. This yielded a robust increase in peripheral and central TNF at P5, and also an increase of additional pro-inflammatory cytokines. Compared to control pups injected with saline, mice injected with TNF acquired the righting and the acoustic startle reflexes more rapidly and exhibited increased locomotor activity 2 weeks after birth. Our results extend previous work restricted to adult behaviors and support the notion that cytokines, and notably TNF, modulate early neurodevelopmental trajectories.

Environmental Enrichment Protects against Neurotoxic Effects of Lipopolysaccharide: A Comprehensive Overview

“…Maternal health during pregnancy plays an important role in determining health and disease risks in the offspring. MIA hypothesis proposes that inflammatory perturbations in utero may affect fetal neurodevelopment [ 17 ] and increase the probability of developing neuropsychiatric, neurological [ 68 ], and neurodevelopmental disorders, such as autism [ 69 ] and schizophrenia [ 70 , 71 ]. Epidemiological studies in humans support the hypothesis that several maternal inflammatory factors, including obesity [ 72 ], psychosocial stress [ 17 ], autoimmune conditions [ 73 ], asthma and allergic conditions [ 74 ], and maternal viral infections [ 75 , 76 , 77 ] may be responsible for MIA [ 78 ].…”