TABLE 5.

Effects of Chronic Isolation Stress model on behaviors, protein, metabolites and genes.

Specific effects of PTSD model on protein, metabolite and/or gene manipulation	Functional effects of PTSD model on protein, metabolite and/or gene or pharmacological manipulation	Region of interest	Behavioral phenotype	PTSD-like effects	Authors and year
CIS increases in ROS accompanied by a decreases in antioxidant GSH	Excess ROS and decreased antioxidant produces molecular and mitochondrial and destruction	Cortex	Increased immobility time in the FST and activated locomotion and rearings in the OFT	Increased depression and anxiety-like behaviors	Haj-Mirzaiana et al., 2016
CIS increased lipid peroxidation products MDA and protein carbonyl groups and reduced antioxidant levels of SOD; Also increased NF-kB protein levels and COX-2 protein levels	Lipid peroxidation effects are a measure of oxidative damage. Reduction in antioxidants leaves cells vulnerable to ROS. Increased NF-kB COX-2 proteins play a role in inflammatory responses	Prefrontal Cortex and Hippocampus	Increased immobility in the FST with reduced climbing and swimming behaviors; Reduced sucrose preference and increased marble burying behavior	Increased depression and anhedonia-like behaviors with increased compulsive behaviors	Zlatkovic et al. (2014)
CIS decreased the oxidative activity of catalase and antioxidants GSH and SOD. CIS Increased ROS and reduced levels of glutamate, glutamine, NAA, and phosphocreatine	Reduced oxidative metabolism and increased ROS damage resulting in metabolism deficits demonstrated by reduced metabolism markers	PFC, Hippocampus, caudatecutamen, cerebellum, thalamus	In the EPM, CIS rats spent more time the closed arms. In social interaction test, CIS rats spent more time with empty cages rather than other rats. In the Y-maze, CIS rats showed lower exploration time	Reduced social interaction and increased anxiety. Reduced motivation to explore	Shao et al. (2015)
CIS reduced mitochondrial enzyme activities. Translocation of Ras from mitochondria to endoplasmic reticulum	During apoptosis translocation of Ras to the mitochondrial occurs which may be involved in switch from oxidative metabolism to anaerobic glycolysis	Hippocampus	In OFT, CIS rats showed less center time	Anxiety-like behaviors	Zhuravliova et al. (2009)
In stress-sensitive rats, CIS induced downregulation of ETC Complex II and Vdac 1 mitochondrial permeability transition pore	CIS reduces ETC enzyme and Vdac1 a key protein involved in regulating the pore opening involved in release of cytochrome c and pro-caspases	Hippocampus	Sucrose preference is reduced and CIS resilient and sensitive rats are defined by SPT functioning. In FST, CIS increased immobility in susceptible rats	Anhedonia-like and depression-like behaviors in susceptible individuals	Peric et al. (2022)
CIS produced reductions in mitochondrial enzymatic activity; CIS increases the ratelimiting enzyme of glycolysis via mitochondrial hexokinase	CIS inhibits mitochondrial oxidative metabolism resulting in a compensatory elevation of anaerobic glycolysis	Hippocampus	Hypoactivity in the OFT	Locomotor slowing	Shuravliova et al., 2009