title: Differential effect of chronic stress on mouse hippocampal memory and affective behavior: Role of major ovarian hormones.
abstract: Molecular mechanisms of depression-like pathophysiology in female rodent models are less reported compared to males, despite its higher prevalence in human females. Moreover, the stress-response in brain circuitries including reward and cognition circuitries varies with age or hormonal status of the females. So, to understand the stress-induced mood and cognitive disorders in intact females (with ovaries) and ovariectomized (OVX) females, we studied changes in mouse hippocampus, a functionally heterogeneous neural structure involved in both affective and cognitive behaviors. Here, we used a 6-day Chronic Unpredictable Stress (CUS) paradigm in mice to induce depression and related mood disorders. Interestingly, intact females and OVX females showed difference in mood disorder sub-phenotypes to CUS. Similar to an earlier report of CUS affecting the critical reward circuitry structure the nucleus accumbens differently in females with and without ovaries, cognitive behavior in intact females and OVX females also responded differentially to CUS, as evident from Morris Water Maze (MWM) test results. We report that the presence or absence of ovarian hormones, particularly the estrogen, has a significant impact in altering the hippocampus related spatial memory and affective behavior, in females. Our results also illustrate that estrogen administration improves both reward and cognitive behavior, and plays a significant role in alleviating stress-induced despair behavior and enhancing spatial reference memory following a brief 6-day stressful paradigm. Further, it also indicates that the NMDA receptor subunits, GRIN2A and GRIN2B, might mediate the effects of estrogen in the hippocampal functions, thus suggestive of a translational significance of the finding.
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Bhanu Chandra
authors: BC
authors: Karisetty
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Swati
authors: S
authors: Maitra
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Abhipradnya Bipin
authors: AB
authors: Wahul
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Anusha
authors: A
authors: Musalamadugu
authors: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Nitin
authors: N
authors: Khandelwal
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Sumasri
authors: S
authors: Guntupalli
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Ramya
authors: R
authors: Garikapati
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Thatiparthi
authors: T
authors: Jhansyrani
authors: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007 Telangana, India.
authors: Arvind
authors: A
authors: Kumar
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Uppal Road, Hyderabad, 500007 Telangana, India. Electronic address: sumana98@gmail.com.
authors: Sumana
authors: S
authors: Chakravarty
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D051379:Mice; D019964:Mood Disorders / Q000150:complications / Q000503:physiopathology*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*
chemical_list: D004958:Estradiol; D011374:Progesterone; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
keywords: 17β-Estradiol; Cognitive disorder; Depression; Mood disorder; NMDAR; Ovariectomy