Transgenerational impairment of hippocampal Akt-mTOR signaling and behavioral deficits in the offspring of mice that experience postpartum depression-like illness.
Postpartum depression (PPD) has adverse effects on offspring and increases their vulnerability to psychiatric disorders such as depression. Akt-mTOR signaling in the hippocampus is implicated in depression but its role in the behavioral deficits in PPD offspring remains unknown. By using a prepregnancy stress model of PPD in which Balb/c females that experience chronic stress before pregnancy show long-lasting PPD-like behaviors, we tested depression-like behaviors in PPD offspring (PPD-F1) at juvenile and adult ages as well as in the second generation (PPD-F2) produced by cross of male PPD-F1 with naïve females. Hippocampal Akt-mTOR signaling was examined in the F1 and F2 generations of PPD, as well as in PPD-F1 mice treated with a single dose of the antidepressant ketamine. PPD-F1 showed depression-like behaviors at juvenile and adult stages, evidenced by reduced sucrose preference (SP), increased immobility time in the forced swim test (FST), and a longer latency to feed and reduced food consumption in the novelty suppressed feeding (NSF) test. PPD-F1 mice showed Akt-mTOR signaling deficiency in the hippocampus, with down-regulated expression of p-Akt, p-mTOR and p-p70S6K. A single dose of ketamine reversed the behavior deficits and the impairment in Akt-mTOR signaling in PPD-F1. Furthermore, the PPD-F2 mice remained deficient in the SP and NSF test and hippocampal Akt-mTOR signaling, although the performance in FST was normal. The present study demonstrated both long-term and transgenerational effects of PPD on the depression-like behaviors of offspring, and suggested impaired Akt-mTOR signaling may play a part.
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China; School of Medicine, Yangzhou University, Yangzhou, China.
Ruyan
R
Wu
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.
Hailou
H
Zhang
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.
Wenda
W
Xue
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.
Zhilu
Z
Zou
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Cai
C
Lu
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China.
Baomei
B
Xia
School of Psychology, Nanjing University of Chinese Medicine, Nanjing, China.
Wei
W
Wang
Center for Translational Systems Biology and Neuroscience, and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: chengang@njucm.edu.cn.
Gang
G
Chen
D000367:Age Factors; D000818:Animals; D019052:Depression, Postpartum; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005518:Food Preferences / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism*; D007649:Ketamine / Q000627:therapeutic use; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D013395:Sucrose; D007649:Ketamine; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases
Akt-mTOR; Depression-like behaviors; Disc1; Offspring; Postpartum depression; Transgeneration