Endogenous Estrogen Influences Predator Odor-Induced Impairment of Cognitive and Social Behaviors in Aromatase Gene Deficiency Mice.

Yaner Gao,Zhengrong Zhang,Rena Li,Feng Gao,Yuhong Li,Zuoli Sun,Lei Ma

doi:10.1155/2021/5346507

Abstract

Epidemiological studies have suggested that traumatic stress increases vulnerability to various mental disorders, such as dementia and psychiatric disorders. While women are more vulnerable than men to depression and anxiety, it is unclear whether endogenous estrogens are responsible for the underlying sex-specific mechanisms. In this study, the aromatase gene heterozygous (Ar+/-) mice were used as an endogenous estrogen deficiency model and age- and sex-matched wild type mice (WT) as controls to study the predator odor 2,3,5-trimethyl-3-thiazoline- (TMT-) induced short- and long-term cognitive and social behavior impairments. In addition, the changes in brain regional neurotransmitters and their associations with TMT-induced changes in behaviors were further investigated in these animals. Our results showed TMT induced immediate fear response in both Ar+/- and WT mice regardless of sexes. TMT induced an acute impairment of novel object recognition memory and long-term social behavior impairment in WT mice, particularly in females, while Ar+/- mice showed impaired novel object recognition in both sexes and TMT-elevated social behaviors, particularly in males. TMT failed to induce changes in the prepulse inhibition (PPI) test in both groups. TMT resulted in a slight increase of DOPAC/DA ratio in the cortex and a significant elevation of this ratio in the striatum of WT mice. In addition, the ratio of HIAA/5-HT was significantly elevated in the cortex of TMT-treated WT mice, which was not found in TMT-treated Ar+/- mice. Taken together, our results indicate that TMT exposure can cause cognitive and social behavior impairments as well as change catecholamine metabolism in WT mice, and endogenous estrogen deficiency might desensitize the behavioral and neurochemical responses to TMT in Ar+/- mice.

Highlights

Epidemiological studies have indicated that dramatic stress in early life may increase the risk for some major psychiatric disorders such as anxiety, major depression, schizophrenia, and posttraumatic stress disorder [1,2,3,4]
To investigate whether endogenous estrogen alters the freezing levels in response to a single Trimethyl-3-Behavioural Neurology thiazoline (TMT) exposure, the freezing time was recorded as previously described [43]
Results showed the freezing levels were significantly higher in both wild type mice (WT) and Ar+/- mice, and there was no significant difference in the TMT-induced freezing time between WT mice and Ar

Summary

Introduction

Epidemiological studies have indicated that dramatic stress in early life may increase the risk for some major psychiatric disorders such as anxiety, major depression, schizophrenia, and posttraumatic stress disorder [1,2,3,4]. Clinical studies have suggested that psychiatric patients with a history of early life stress often have more severe psychotic symptoms as well as impaired brain functions [5, 6]. Accumulating evidence suggests that TMT exposure is suitable to investigate the uncontrollable stress responses in rodents [14, 15], such as the activation of a distinct neural circuit in various brain regions in stress response [14], the activation of hypothalamus-pituitary-adrenal (HPA) axis [16, 17], and induction of reliable fearful responses as freezing, diminished grooming behaviors, and decreased exploratory behavior [18, 19]. The effects of predator stress on the anxiety behaviors are still controversial as a delayed attenuation of anxiety in juvenile mice [21] and an increased anxiety in adolescence rats [8]

Methods

Results

Discussion

Conclusion