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Modification of female and male social behaviors in estrogen receptor beta knockout mice by neonatal maternal separation.

Tsuda MC, Yamaguchi N, Nakata M, Ogawa S - Front Neurosci (2014)

Bottom Line: Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors.However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes.On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral Neuroendocrinology, University of Tsukuba Tsukuba, Japan.

ABSTRACT
Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO) mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT) mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h) from postnatal day 1-14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression.

No MeSH data available.


Related in: MedlinePlus

MS effects on peri-pubertal and adult male aggression. (A–C) Peri-pubertal and (D–F) adult WT and βERKO male mice. (A,D) Number of aggressive bouts, (B,E) cumulative duration of aggression, and (C,F) latency to the first aggressive bout. All data are presented as mean ± s.e.m. *p < 0.05.
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Figure 4: MS effects on peri-pubertal and adult male aggression. (A–C) Peri-pubertal and (D–F) adult WT and βERKO male mice. (A,D) Number of aggressive bouts, (B,E) cumulative duration of aggression, and (C,F) latency to the first aggressive bout. All data are presented as mean ± s.e.m. *p < 0.05.

Mentions: Peri-pubertal male aggressive behaviors were greatly suppressed by MS stress in both βERKO and WT mice at 5 and 6 weeks of age. There was a significant main effect of MS and age on the number of aggressive bouts ([treatment: F(1, 29) = 11.03, p < 0.01; age: F(1, 29) = 23.95, p < 0.0001]; Figure 4A), cumulative duration of aggression ([treatment: F(1, 29) = 10.37, p < 0.01; age: F(1, 29) = 10.82, p < 0.01]; Figure 4B), and latency to the first aggressive bout ([treatment: F(1, 29) = 3.14, p = 0.09; age: F(1, 29) = 17.45, p < 0.01]; Figure 4C), in which aggression levels were greater at 6 weeks of age compared to 5 weeks. However, no effect of genotype or interactions was found in all three behavioral measurements.


Modification of female and male social behaviors in estrogen receptor beta knockout mice by neonatal maternal separation.

Tsuda MC, Yamaguchi N, Nakata M, Ogawa S - Front Neurosci (2014)

MS effects on peri-pubertal and adult male aggression. (A–C) Peri-pubertal and (D–F) adult WT and βERKO male mice. (A,D) Number of aggressive bouts, (B,E) cumulative duration of aggression, and (C,F) latency to the first aggressive bout. All data are presented as mean ± s.e.m. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151037&req=5

Figure 4: MS effects on peri-pubertal and adult male aggression. (A–C) Peri-pubertal and (D–F) adult WT and βERKO male mice. (A,D) Number of aggressive bouts, (B,E) cumulative duration of aggression, and (C,F) latency to the first aggressive bout. All data are presented as mean ± s.e.m. *p < 0.05.
Mentions: Peri-pubertal male aggressive behaviors were greatly suppressed by MS stress in both βERKO and WT mice at 5 and 6 weeks of age. There was a significant main effect of MS and age on the number of aggressive bouts ([treatment: F(1, 29) = 11.03, p < 0.01; age: F(1, 29) = 23.95, p < 0.0001]; Figure 4A), cumulative duration of aggression ([treatment: F(1, 29) = 10.37, p < 0.01; age: F(1, 29) = 10.82, p < 0.01]; Figure 4B), and latency to the first aggressive bout ([treatment: F(1, 29) = 3.14, p = 0.09; age: F(1, 29) = 17.45, p < 0.01]; Figure 4C), in which aggression levels were greater at 6 weeks of age compared to 5 weeks. However, no effect of genotype or interactions was found in all three behavioral measurements.

Bottom Line: Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors.However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes.On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral Neuroendocrinology, University of Tsukuba Tsukuba, Japan.

ABSTRACT
Maternal separation (MS) is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER) β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO) mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT) mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h) from postnatal day 1-14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression.

No MeSH data available.


Related in: MedlinePlus