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Original Article

Neonatal immune activation during early and

late postnatal brain development differently

influences depression‑related behaviors in

adolescent and adult C57BL/6 mice

1
2
1
1
Jafar Majidi-Zolbanin , Mohammad-Hossein Doosti , Behzad Baradaran , Mohammad Amani ,
Maryam Azarfarin , Ali-Akbar Salari 3,4
3
1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51639, East Azerbaijan, Iran.
2 Department of Physiology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil 55136, Ardabil, Iran.
3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51639, East Azerbaijan, Iran.
4 Laboratory of Neuropsychopharmacology and Psychoneuroimmunology, Hayyan Research Institute, University of Tabriz, Tabriz
51639, East Azerbaijan, Iran.
ABSTRA CT
Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions,
resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition,
previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study
aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C)
during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male
C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg) on postnatal days (PND) 3–5 (early neonatal phase)
or PND 14–16 (late neonatal phase), and then subjected to behavioral tests, including tail suspension test and forced swimming test,
during adolescence (PND 35 or 40) and adulthood (PND 85 or 90). Results: The results demonstrated that early neonatal immune
activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases
depression in adult mice. In other words, these findings indicated that the nature of the offspring’s neuropathology can depend on the
severity of the insult, the pup’s age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These
findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric
disorders in adults who experienced early life infection.

Key words: Age, depression, hypothalamic-pituitary-adrenal axis, mice, neonatal infection, Poly I:C

INTRODUCTION increase susceptibility to the onset of neuropsychiatric
disorders, such as anxiety and depression, later in
Many studies have recently demonstrated the life. [1-7] Lipopolysaccharide (LPS, mimics bacterial
importance of early life infection on the brain and infection) and polyinosinic-polycytidylic acid
behavior development, and how such infections can (Poly I:C, mimics viral infection) administration during
the neonatal period are known as two animal models
Access this article online of neonatal infection, and both can stimulate the
Quick Response Code: immune and endocrine systems. We and others have
[8]
Website: shown that LPS- or Poly I:C-induced neonatal infection
www.nnjournal.net
can lead to hypothalamic-pituitary-adrenal (HPA) axis
DOI: abnormalities and results in increased anxiety- and
10.4103/2347-8659.135575 depression-like behaviors in adult rodents. [6,7,9]

Corresponding Author: Mr. Ali‑Akbar Salari, Laboratory of Neuropsychopharmacology and Psychoneuroimmunology,
Hayyan Research Institute, University of Tabriz, Tabriz 51639, East Azerbaijan, Iran. E‑mail: aa.salari@yahoo.com

Neuroimmunol Neuroinflammation | Volume 1 | Issue 1 | June 2014 35