title: Neuropsin Inactivation Has Protective Effects against Depressive-Like Behaviours and Memory Impairment Induced by Chronic Stress.
abstract: Mounting evidence suggests the interaction between stress and genetics contribute to the development of depressive symptoms. Currently, the molecular mechanisms mediating this process are poorly understood, hindering the development of new clinical interventions. Here, we investigate the interaction between neuropsin, a serine protease, and chronic stress on the development of depressive-like behaviours in mice. We found no difference in baseline behaviour between neuropsin knockout and wild-type mice. However, our results show that neuropsin knockout mice are protected against the development of depressive-like behaviours and memory impairment following chronic stress. We hypothesised that this difference in behaviour may be due to an interaction between neuropsin and elevated plasma corticosterone. To test this, we subjected mice to chronic corticosterone injections. These injections resulted in changes to hippocampal structure similar to that observed following chronic stress. We found that inactivation of neuropsin limits the extent of these anatomical changes in both the chronic stress and the corticosterone injection exposed cohorts. We next used viral vectors to knockdown or overexpress neuropsin in the hippocampus to confirm the results of the KO study. Additionally, we found that inactivation of neuropsin limited glutamate dysregulation, associated with increased generation of reactive oxygen species, resulting from prolonged elevated plasma corticosterone. In this study, we demonstrate that neuropsin inactivation protects against the impairment of hippocampal functions and the depressive-like behaviour induced by chronic stress or high levels of corticosterone. Consequently, we suggest neuropsin is a potential target for clinical interventions for the management of stress disorders.
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Simon
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Philane
authors.initials: P
authors.lastname: Bok
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Cheng-Pu
authors.initials: CP
authors.lastname: Sun
authors.affiliation: Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Edwards
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood; D003863:Depression / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007610:Kallikreins / Q000097:blood / Q000235:genetics*; D008569:Memory Disorders / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology
chemical_list: D018698:Glutamic Acid; D007610:Kallikreins; C114664:Prss19 protein, mouse; D003345:Corticosterone