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In addition, we found high levels of depression-related
behaviors in adulthood in Poly I:C-exposed mice
compared with saline-injected mice.

Effects of early and late neonatal immune activation on
depression-related behaviors during adolescence and
adulthood in the FST
The three-way analysis indicated the significant effects a b
of the time of postnatal immune activation (F 1,84 =34.69, Figure 3: Effects of late neonatal immune challenge on depression-like behavior

P < 0.001), age (F 1,4 = 20.37, P < 0.001), and during adolescence (a) and adulthood (b) in the tail suspension test. The data
are presented as mean ± standard error of the mean (n = 8). *P < 0.05 compared

treatment (F 2,84 = 20.53, P < 0.001) on the immobility to the saline-treated group

time in the FST. Considerable interactions
existed between the time of neonatal immune
activation × treatment (F 2,84 = 5.02, P < 0.009) and

age × treatment (F 2,84 =5.77, P < 0.005). However, there

was no interaction between the time of neonatal immune
activation × age and the time of neonatal immune
activation × age × treatment. These data demonstrate
that immune activation with Poly I:C during postnatal a b
brain development can affect depression-related
behaviors in dose-, age-, and time-dependent manner Figure 4: Impacts of early postnatal immune activation on depression-like
behavior during adolescence (a) and adulthood (b) in the forced swimming test.
in adult mice. Thus, these different factors may affect The data are presented as mean ± standard error of the mean (n = 8). *P < 0.05,
the effects of neonatal immune activation on affective **P < 0.01, and ***P < 0.001 compared to the saline-treated group
disorders later in life in animal models.

The results of the FST assessment showed that early
postnatal immune activation with Poly I:C increased
immobility time at the dose of 4 mg/kg during
adolescence [Figure 4a; P = 0.015] and at both doses
in adulthood [Figure 4b; P = 0.002 and P = 0.000].
Higher levels of depression-related behaviors were a b
measured in Poly I:C-treated mice in comparison with Figure 5: Effects of late neonatal immune activation on depression-like behavior
the saline-treated group. during adolescence (a) and adulthood (b) in the forced swimming test. The data
are presented as mean ± standard error of the mean (n = 8). *P < 0.05, compared
to the saline-treated group
Our data also showed that immune activation with
4 mg/kg Poly I:C during late neonatal brain development physiological, behavioral, and neuroendocrine systems
increased the total duration of immobility in in adulthood. [6,8,9] For instance, it has been reported
adulthood (P = 0.019), but not in adolescence [Figure 5], that bacterial and viral infections during early [9,11] and
indicating high levels of depression-related behaviors late [15] neonatal periods results in increased anxiety-like
during adulthood in Poly I:C-exposed mice relative to behaviors and disrupted HPA axis activity in adult
the saline-treated group. These results confirmed that rodents. Our results demonstrated that early neonatal
time of postnatal immune challenge, age and the dose immune activation led to increased depression-related
of immunogen can be important factors for evaluating behaviors in both adolescent and adult mice, but late
depression-related behaviors in mice. neonatal infection only increased depression in adult
mice. In this regard, Konat et al. [15] showed that anxiety
DISCUSSION levels in rats following late postnatal immune activation
were much larger than those observed by Ibi et al. [17]
We recently showed that early postnatal immune in mice following early neonatal immune challenge
challenge with the bacterial endotoxin and LPS can using a similar behavioral testing. Previous studies
lead to increased levels of corticosterone (COR) and demonstrated that early postnatal immune challenge
depression-like symptoms in adult male and female increased baseline COR levels during adolescence and
[6]
NMRI mice. In addition, early postnatal immune adulthood, while late neonatal immune activation did
challenge has been shown to have adverse outcomes on not alter baseline COR levels in adulthood. [18] It was

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