TABLE 3.

Effects of protein/gene manipulation on Fear Learning Models.

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
Bax protein (Bcl-2-associated X protein) knock out in mice	Bax protein acts as apoptotic regulators. LTD. in FC mice is eliminated	Hippocampus	FC was reduced in BAX KO mice and 24 h later mice reduced fear expression to the training context	Reduced fear learning	Xing Liu et al., 2014
Disrupted-In-Schizophrenia-1 (DISC1) gene knockdown decreased astrocytes and mitochondrial markers. DISC1 KD reduced glutamate transporter and glutamatergic markers and increased GABAergic synaptic markers	DISC1 gene knockdown reduced mitochondrial markers and reduced glutamatergic transmission and increased GABAergic transmission	Hippocampus	Impaired expression of cue-induced fear conditioning	Reduced cueinduced fear learning	Shevelkin et al. (2020)
Glutaminase overexpression increased astrocyte and microglia markers, inflammatory factors and decreased synaptophysin	Glutaminase overexpression decreased hippocampal LTP and induced apoptotic neuroinflammatory and synaptic changes	Hippocampus and Frontal Cortex	Reductions in fear expression	Fear learning deficits	Wang et al. (2017)
Treatment with DF302 reduced calcium-induced mitochondria swelling, potentiated AMPA receptormediated currents, inhibited mitochondrial permeability	Reduction in neurodegeneration through several mechanisms	Hippocampus	In the contextual FC test, mice treated with DF302 showed longer freezing times. DF302 also reduced aggression between males and reduced immobility in the FST.	Compound increases fear learning and has antidepressant and anti-aggression effects	Strekalova et al., 2018
Cisplatin treatment produces mtDNA damage and impairs ETC respiratory activity; treatment increases mitochondrial degradation and vacuolization and increases apoptotic neurons	Cisplatin induces mtDNA damage and oxidative stress, mitochondrial degradation, and apoptosis	Hippocampus	Reduced expression of contextual FC	Reduces fear learning	Lomeli et al. (2017)
Contextual FC produces differential gene expression including for translocase of outer mitochondrial membrane 20 protein	FC altered gene expression of protein important mitochondrial morphology	Frontal Cortex	Contextual FC model produced altered gene expression	Fear learning model	Federighti et al. (2013)
Overexpression of mitochondrial catalase which regulates ROS and oxidative metabolism	Catalase activity was elevated along with increased parameters of oxidative stress	Frontal Cortex	Increased FC and time on open arm of EPM	Increased fear learning but reduced anxiety	Olsen et al. (2013)
Haploinsufficiency of FOXP1 gene disrupts mitochondria fusion and fission; it increases mitophagy, oxidative stress, cytochrome c release, and apoptosis	Haploinsuffience of FOXPI gene produced disruption of mitochondrial functions replication, and increases autophagy, oxidative stress, and apoptosis	Hippocampus	Reductions in expression of contextual and cued FC	Reduces Fear Learning	Wang et al. (2022)