Abstract:
Background: Early life stress is correlated with escalated peril for anxiety, mood, substance, impulse control and depressive disorders. Such disorders might spring from chemical imbalance in brain. A well-grounded mouse prototype of childhood adversity contributing to the everlasting behavioral changes in an individual would help understand the mechanism underlying these adverse effects. Maternal deprivation is frequently used paradigm of early neglect. Natriuretic peptides especially Atrial Natriuretic Peptide (ANP) released from Atrial myocytes have significant anxiolytic role corroborated by certain animal and human trails. The concentration of ANP has been found to be elevated by Levothyroxine (LT4) which treats the adverse symptoms of anxiety and depression.
Method and Results: In an attempt to contrive the paradigm of childhood adversity in mouse models with everlasting impacts on behavior of balb/c mice, maternal separation model followed by early weaning model were developed and behavioral tests were performed 60 days following maternal separation followed by early weaning (MSEW) paradigm for the validation of model. The experimental and control groups were further divided into 3 groups: MSEW group with drug administration, MSEW group with no drug administration and control group with no MSEW and no drug administration. Following a 7 days administration of LT4 at the concentration of 15 micrograms per mice to MSEW group and one of the control groups, decline in anxiety level in mice subjected to MSEW was observed in comparison to the MSEW group that was not administered LT4. These findings were validated by performing anxiety related paradigms after drug injection and the difference in the behavior was observed accordingly which suggested decrease in behavioral despair and anxiety related symptoms in mice.
Conclusion: Our findings elucidate that maternal separation model followed by early weaning contributes as a substantial paradigm to scrutinize the intricate behavioral anomalies in organisms with early life adversity history and by increasing the concentration of ANP by injection of LT4 cures the anxiety-related symptoms and provides a n apprehension for a futuristic therapeutic plan of actions.
