| Full text | |
| Author(s): |
Santos-Silva, Thamyris
;
Lopes, Caio Fabio Baeta
;
Hazar Ulgen, Dogukan
;
Guimaraes, Danielle A.
;
Guimaraes, Francisco S.
;
Alberici, Luciane Carla
;
Sandi, Carmen
;
Gomes, Felipe, V
Total Authors: 8
|
| Document type: | Journal article |
| Source: | SCHIZOPHRENIA BULLETIN; v. N/A, p. 12-pg., 2024-03-25. |
| 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. (AU) | |
| FAPESP's process: | 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders |
| Grantee: | Francisco Silveira Guimaraes |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/17597-3 - The impact of stress on the dopamine system depends on the state of the critical period of neuroplasticity: implications for depression and schizophrenia and for the study of new drug targets |
| Grantee: | Felipe Villela Gomes |
| Support Opportunities: | Research Grants - Young Investigators Grants |