We investigated the levels of expression of caspase-3 and 9 in the medial prefrontal cortex (mPFC) of rats subjected to single prolonged stress (SPS) to provide a novel insight into the mechanism of how this cortical region is related to post-traumatic stress disorder (PTSD). Fifty male Wistar rats were divided into the control group and four SPS groups examined at days 1, 4, 7, and 14 after treatment. Expression of caspase-3 in SPS groups was significantly greater when compared with the control group (P < 0.05) and peaked at day 7 after exposure to SPS. In the control group, the intensity of fluorescence of caspase-9-positive cells was low, while that in the SPS groups was significantly higher (P < 0.01) and peaked at day 4 after exposure to SPS. After SPS episodes, levels of mRNA of caspase-3 and caspase-9, compared with those in the control group, gradually increased and peaked at days 7 and 4, respectively (P < 0.01). Therefore, changes of expression of caspase-9 and caspase-3 may play an important role in the pathogenesis of PTSD.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV, Am. Psychiat. Press, Washington (1994).
L. Cahill and J. L. McGaugh, “Mechanisms of emotional arousal and lasting declarative memory,” Trends Neurosci., 21, No. 7, 294-299 (1998).
V. Cryns and J. Yuan, “Proteases to die for,” Genes Dev., 12, No. 11, 1551-1570 (1998).
H. Cui, H. Sakamoto, S. Higashi, and M. Kawata, “Effects of single-prolonged stress on neurons and their afferent inputs in the amygdala,” Neuroscience, 152, No, 3, 703-712 (2008).
E. R. de Kloet, “Stress: a neurobiological perspective,” Tijdschr. Psychiat., 51, No. 8, 541-550 (2009).
E. Vermetten, “Stress, trauma, and post-traumatic stress disorder,” Tijdschr. Psychiat., 51, No. 8, 595-602 (2009).
J. E. LeDoux, “Emotion: clues from the brain,” Annu. Rev. Psychol., 46, 209-235 (1995).
J. L. McGaugh and L. Cahill, “Interaction of neuromodulatory systems in modulating memory storage,” Behav. Brain Res., 83, Nos. 1/2, 31-38 (1997).
A. J. McDonald, F. Mascagni, and L. Guo, “Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat,” Neuroscience, 71, No. 1, 55-75 (1996).
L. M. Shin and I. Liberzon, “The Neurocircuitry of fear, stress, and anxiety disorders,” Neuropsychopharmacology, 35, No. 1, 169-191 (2009).
Y. Iwamoto, S. Morinobu, T. Takahashi, and S. Yamawaki, “Single prolonged stress increases contextual freezing and the expression of glycine transporter 1 and vesicle-associated membrane protein 2 mRNA in the hippocampus of rats,” Prog. Neuropsychopharmacol. Biol. Psychiat., 31, No. 3, 642-651 (2007).
S. Khan and I. Liberzon, “Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD,” Psychopharmacology, 172, No. 2, 225-229 (2004).
T. Takahashi, S. Morinobu, Y. Iwamoto, and S. Yamawaki, “Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats,” Psychopharmacology, 189, No. 2, 165-173 (2006).
H. F. Figueiredo, A. Bruestle, B. Bodie, et al., “The medial prefrontal cortex differentially regulates stressinduced c-fos expression in the forebrain depending on type of stressor,” Eur. J. Neurosci., 18, No. 8, 2357-2364 (2003).
J. J. Radley, C. M. Arias, and P. E. Sawchenko, “Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress,” J. Neurosci., 26, No. 50, 12967-12976 (2006).
G. Paxinos, C. Watson, and P. C. Emson, “AChEstained horizontal sections of the rat brain in stereotaxic coordinates,” J. Neurosci. Methods, 3, No. 2, 129-149 (1980).
J. L. McGauqh, “The amygdala modulates the consolidation of memories of emotionally arousing experience,” Annu. Rev. Neurosci., 27, 1-28 (2004).
E. A. Phelps, M. R. Delgado, K. I. Nearing, and J. E. LeDoux, “Extinction learning in humans: role of the amygdala and vmPFC,” Neuron, 43, No. 6, 897-905 (2004).
M. D. De Bellis, M. S. Keshavan, H. Shifflett, et al., “Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study,” Biol. Psychiat., 52, No. 11, 1066-1078 (2002).
C. Fennema-Notestine, M. B. Stein, C. M. Kennedy, et al., “Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder,” Biol. Psychiat., 52, No. 11, 1089-1101 (2002).
W. C. Eamshaw, L. M. Martins, and S. H. Kaufmann, “Mammalian caspases: structure, activation, substrates, and functions during apoptosis,” Annu. Rev. Biochem., 68, 383-424 (1999).
D. R. Green and J. C. Reed, “Mitochondria and apoptosis,” Science, 281, 1309-1312 (1998).
G. Nunez, M. A. Benedict, Y. Hu, and N. Inohara, “Caspases: the proteases of the apoptotic pathway,” Oncogene, 17, No. 25, 3237-3245 (1998).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Zhang, J.H., Li, M., Han, F. et al. Stress-Induced Increases in Levels of Caspases in the Prefrontal Cortex in a Rat Model of PTSD. Neurophysiology 48, 11–16 (2016). https://doi.org/10.1007/s11062-016-9563-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11062-016-9563-0