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Updated: Sep 28, 2025
Neurodevelopmental Reflex Testing in Neonatal Rat Pups
Published on: April 24, 2017
Early Life Exposure to Tumor Necrosis Factor Induces Precocious Sensorimotor Reflexes Acquisition and Increases
Cristina Paraschivescu1, Susana Barbosa1, Juliette Van Steenwinckel2
1Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, Valbonne, France.
Insights
Early life exposure to Tumor Necrosis Factor (TNF), a pro-inflammatory cytokine, accelerates neurodevelopment and enhances motor activity in mouse pups. This suggests TNF influences early brain development and behavior.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Inflammation and immune activation during early life are linked to neurodevelopmental and psychopathological outcomes.
- Pro-inflammatory cytokines, such as Tumor Necrosis Factor (TNF), play roles in both homeostasis and neurodevelopment.
- The specific impact of TNF on immediate postnatal neurodevelopmental trajectories remains unclear.
Purpose of the Study:
- To investigate the effects of early postnatal administration of recombinant TNF on neurodevelopmental trajectories and behavior in mice.
- To determine if elevated TNF levels during the critical early postnatal period alter motor reflex acquisition and activity levels.
Main Methods:
- Mouse pups were injected daily with recombinant TNF from postnatal day 1 to 5.
- Peripheral and central TNF levels were measured at postnatal day 5.
- Acquisition of righting and acoustic startle reflexes, and locomotor activity were assessed.
Main Results:
- TNF injections led to increased peripheral and central TNF levels, along with elevated pro-inflammatory cytokines.
- TNF-treated pups showed accelerated acquisition of righting and acoustic startle reflexes compared to controls.
- Increased locomotor activity was observed in TNF-treated mice two weeks after birth.
Conclusions:
- Early postnatal exposure to TNF significantly modulates neurodevelopmental trajectories in mice.
- Elevated TNF levels during the immediate postnatal period enhance motor reflex development and locomotor activity.
- These findings highlight the critical role of cytokines, particularly TNF, in shaping early brain development and behavior.
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.
