TABLE 7.

Effects of Chronic Restraint Stress or Single Prolonged Stress models 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
CRS reduced ETC Complexes I, II, III, IV	Reduction of Complexes critical to mitochondrial ETC function and cellular respiration	Hippocampus, and Frontal Cortex	Sucrose preference was reduced on weeks 2, 3, and 4 of CRS	Increase in anhedonialike behaviors	Aboul-Fouh 2013
Mitochondrial unfolded protein response (UPRmt) is a stress response that activates the transcription of mitochondrial chaperones; CRS induced upregulation of UPRmt and reduced oxygen consumption	CRS-induced promotion of protein homeostasis and reduced oxidative metabolism	Forebrain	CRS induced depressive-like immobility in both the TST and FST	Increase in depressiomnlike behavioirs	Kembe and Miyata (2015)
In a gene enrichment analysis, CRS produced altered mitochondrial energy synthesis pathways such as “oxidative phosphorylation”, “aerobic electron transport chain”, and “mitochondrial electron transport”; CRS induced upregulation of mtDNA encoded genes of the ETC Complexes I, III and IV and reduced mitochondrial respiration	Stress-induced alterations in PFC “oxidative phosphorylation” explained behavioral changes after CRS	PFC and Nucleus Accumbens	CRS mice reduced time spent in social interaction, increased social avoidance, increased immobility in the FST	Increase in anxiety and social avoidance	Wegner et al. (2020)
CRS decreased MnSOD expression was detected in and increased mitochondrial fission protein	Decreases in MnSOD protection from ROS damage. Increased mitochondrial fission to respond to stress	Hippocampus and Prefrontal Cortex	CRS increased immobility time compared to controls. Results in MWM, indicated the CRS rats required more time to find the hidden platform than the control group	Increase in depressionrelated behaviors and cognitive impairments	Suwanjang et al. (2021)
CRS increased ROS and reduced antioxidant levels of GSH, MDA and total antioxidant capacity. CRS increased inflammatory responses of TNF-α and NF-κB and IL-1β of mitochondrial fractions. CRS disrupted MMP, and increased Bax/Bcl-2 ratio and release of cytochrome c from mitochondria. CRS increased cleavage of procaspase 9 and pro-caspase 3	CRS produced mitochondrial dysfunctions in MMP, oxidative stress, neuroinflammation, and neuronal apoptosis. CRS also shifted the balance of oxidant and antioxidant components	PFC and Hippocampus	CRS reduced the open arm time and entries in the EPM and increased immobility time in TST and FST	Increased anxiety- and depressive-like behaviors	Salehpour et al. (2019)
CRS produced increases in oxidative stress markers, MDA and glutathione, and reduced antioxidants glutathione SOD and catalase activity. CRS reduced activities of ETC complexes I–IV. CRS reduced activation Nrf2 pathway, an orchestrated gene expression of enzymes involved in oxidative defense	CRS reduced ETC chain proteins, increased oxidative markers, reduced antioxidants and decreased an oxidative defense protein	Hippocampus	CRS reduced the percentage of sucrose solution in SPT. In OFT CRS decreased the number of open field crossings and entrances into the central zone. CRS also increased stereotypic behaviors, grooming and rearing compared in the OFT. In the FST, CRS reduced swimming time, struggling time and increased immobility time	Increase in anxiety- and depression-like behaviors	Abuelez et al. (2018)
CRS produced damage mitochondrial structure, and induced agglutination and reduction of synaptic vesicles; CRS decreased number of total synapses, axo-dendritic synapses, presynaptic terminals and increased presynaptic terminals with granular synaptic vesicles	CRS produced mitochondrial structural damage and reduced axo-dendritic synapses and presynaptic synaptic terminals	CNA	In the EPM, CRS increased rearing and grooming stereotyped behaviors and reduced open and center arms entry/time; CRS increased entries and time in closed arms	Increased anxiety-like behaviors	Zhavnia et al., 2022
SPS group showed marked swelling of mitochondria and crista degranulation; SPS produced apoptosis markers in neurons with iron accumulation	SPS produces mitochondrial degradation, apoptosis and iron accumulation	Hippocampus, and Prefrontal Cortex	In the EPM, SPS reduced open arm time and distance and arm entries. In the OFT, SPS rats showed reductions in central time and total distance	Increased anxiety-like behaviors	Zhao et al. (2016)
SPS reduced mitochondrial respiration in ETC Complexes II, III, and V and reduced MMP	SRS reduced mitochondrial bioenergetics, mitochondrial enzyme activities, and MMP	Prefrontal Cortex	SPS and repeated FC produced freezing behavior. In EPM, time spent/entries in the open arm were decreased; In Ymaze, exploratory behavior was reduced	Increases in fear- and anxiety-like and reductions in exploratory behaviors	Bhattacharhee et al. (2021)