Affiliation:
1. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil
2. Department of Biomolecular Sciences, Ribeirão Preto Pharmaceutical Sciences School, University of São Paulo , Ribeirão Preto , Brazil
3. Brain Mind Institute, École Polytechnique Fédérale de Lausanne , Lausanne , Switzerland
Abstract
Abstract
Background and Hypothesis
Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood.
Study Design
After exposing adolescent animals to physical stress (postnatal day, PND31–40), we explored social and cognitive behaviors (PND47–49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum.
Study Results
Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress.
Conclusions
Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ.
Funder
São Paulo Research Foundation
International Brain Research Organization
Coordination for the Improvement of Higher Education Personnel—Brazil
CAPES
Swiss National Science Foundation
EPFL
Publisher
Oxford University Press (OUP)
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献