Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats
Само за регистроване кориснике
2011
Аутори
Radojčić, MarijaAdžić, Miroslav
Nićiforović, Ana
Đorđević, Jelena
Đorđević, Ana
Demonacos, Constantinos
Krstić-Demonacos, Marija
Поглавље у монографији (Објављена верзија)
,
Nova Science Publishers, Incorporated
Метаподаци
Приказ свих података о документуАпстракт
Chronic stress is recognized as an etiological factor for the onset and exacerbation of
many psychiatric disorders. Among chronic stressors, those of psychosocial and
emotional origin are considered of particular importance for prominent depletion of
physiological and psychological resources. The key mechanisms underlying deleterious
effects of chronic stress are thought to emerge from the compromised stress response at
the level of hypothalamic-pituitary-adrenal (HPA) axis feedback, and limbic brain
structures, such as hippocampus (HIPPO) and prefrontal cortex (PFC).
In this review we summarize and discuss effects of chronic psychosocial isolation
(CPSI) using animal model of male Wistar rats, housed individually for 21 days lacking
physical and visual contact. CPSI, as an important distress factor for normally gregarious
Wistar rats, resulted in diminishment of serum corticosterone and blood glucose, and did
not alter catecholamine levels, which opposes most other chronic ...stressors that elevate
stress hormones. In the context of possibly aberrant feedback mechanism at the molecular
level, we discuss altered glucocorticoid receptor (GR) distribution and appearance of GR
phosphoisoform excessively phosphorylated on serine 232 (pGR S232), as well as,
altered activities of JNK and CDK kinases that target GR for phosphorylation. The
appearance of pGR S232 in the nucleus and the mitochondria of HIPPO and PFC is
potentially related to a marked transcriptional activation/repression of several GR
regulated nuclear genes (GR itself, CRH, BDNF) and mitochondrial genes (COX1,
COX3). Another important stress and redox state sensitive transcription factor, nuclear factor kappa B (NFțB) is also discussed in terms of the disturbed redox balance
(illustrated by the altered ratio of the activity of an array of antioxidant enzymes) and
altered proapoptotic/proplastic signalling, since it regulates transcription of a wide array
of genes (like Bcl-2, NCAM). Such cellular conditions, provoked by CPSI, are also
shown to affect susceptibility to mitochondrially triggered apoptosis (illustrated by
redistribution of Bcl family members and DNA fragmentation, more prominent in the
PFC) and to simultaneously affect expression of main neural plasticity protein,
polysialylated NCAM (PSA-NCAM). In summary, we present novel causal connection
between the redox imbalance in the CNS, altered signalling via JNK and CDK kinases,
GR phosphorylation/transactivity and NFțB transactivity, as well as their cellular
imbalance, the parameters which all together yield inadequate CNS and systemic stress
response.
Извор:
Horizons in Neuroscience Research, 2011, 5, 97-126Колекције
Институција/група
VinčaTY - CHAP AU - Radojčić, Marija AU - Adžić, Miroslav AU - Nićiforović, Ana AU - Đorđević, Jelena AU - Đorđević, Ana AU - Demonacos, Constantinos AU - Krstić-Demonacos, Marija PY - 2011 UR - https://vinar.vin.bg.ac.rs/handle/123456789/12040 AB - Chronic stress is recognized as an etiological factor for the onset and exacerbation of many psychiatric disorders. Among chronic stressors, those of psychosocial and emotional origin are considered of particular importance for prominent depletion of physiological and psychological resources. The key mechanisms underlying deleterious effects of chronic stress are thought to emerge from the compromised stress response at the level of hypothalamic-pituitary-adrenal (HPA) axis feedback, and limbic brain structures, such as hippocampus (HIPPO) and prefrontal cortex (PFC). In this review we summarize and discuss effects of chronic psychosocial isolation (CPSI) using animal model of male Wistar rats, housed individually for 21 days lacking physical and visual contact. CPSI, as an important distress factor for normally gregarious Wistar rats, resulted in diminishment of serum corticosterone and blood glucose, and did not alter catecholamine levels, which opposes most other chronic stressors that elevate stress hormones. In the context of possibly aberrant feedback mechanism at the molecular level, we discuss altered glucocorticoid receptor (GR) distribution and appearance of GR phosphoisoform excessively phosphorylated on serine 232 (pGR S232), as well as, altered activities of JNK and CDK kinases that target GR for phosphorylation. The appearance of pGR S232 in the nucleus and the mitochondria of HIPPO and PFC is potentially related to a marked transcriptional activation/repression of several GR regulated nuclear genes (GR itself, CRH, BDNF) and mitochondrial genes (COX1, COX3). Another important stress and redox state sensitive transcription factor, nuclear factor kappa B (NFțB) is also discussed in terms of the disturbed redox balance (illustrated by the altered ratio of the activity of an array of antioxidant enzymes) and altered proapoptotic/proplastic signalling, since it regulates transcription of a wide array of genes (like Bcl-2, NCAM). Such cellular conditions, provoked by CPSI, are also shown to affect susceptibility to mitochondrially triggered apoptosis (illustrated by redistribution of Bcl family members and DNA fragmentation, more prominent in the PFC) and to simultaneously affect expression of main neural plasticity protein, polysialylated NCAM (PSA-NCAM). In summary, we present novel causal connection between the redox imbalance in the CNS, altered signalling via JNK and CDK kinases, GR phosphorylation/transactivity and NFțB transactivity, as well as their cellular imbalance, the parameters which all together yield inadequate CNS and systemic stress response. T2 - Horizons in Neuroscience Research T1 - Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats VL - 5 SP - 97 EP - 126 UR - https://hdl.handle.net/21.15107/rcub_vinar_12040 ER -
@inbook{ author = "Radojčić, Marija and Adžić, Miroslav and Nićiforović, Ana and Đorđević, Jelena and Đorđević, Ana and Demonacos, Constantinos and Krstić-Demonacos, Marija", year = "2011", abstract = "Chronic stress is recognized as an etiological factor for the onset and exacerbation of many psychiatric disorders. Among chronic stressors, those of psychosocial and emotional origin are considered of particular importance for prominent depletion of physiological and psychological resources. The key mechanisms underlying deleterious effects of chronic stress are thought to emerge from the compromised stress response at the level of hypothalamic-pituitary-adrenal (HPA) axis feedback, and limbic brain structures, such as hippocampus (HIPPO) and prefrontal cortex (PFC). In this review we summarize and discuss effects of chronic psychosocial isolation (CPSI) using animal model of male Wistar rats, housed individually for 21 days lacking physical and visual contact. CPSI, as an important distress factor for normally gregarious Wistar rats, resulted in diminishment of serum corticosterone and blood glucose, and did not alter catecholamine levels, which opposes most other chronic stressors that elevate stress hormones. In the context of possibly aberrant feedback mechanism at the molecular level, we discuss altered glucocorticoid receptor (GR) distribution and appearance of GR phosphoisoform excessively phosphorylated on serine 232 (pGR S232), as well as, altered activities of JNK and CDK kinases that target GR for phosphorylation. The appearance of pGR S232 in the nucleus and the mitochondria of HIPPO and PFC is potentially related to a marked transcriptional activation/repression of several GR regulated nuclear genes (GR itself, CRH, BDNF) and mitochondrial genes (COX1, COX3). Another important stress and redox state sensitive transcription factor, nuclear factor kappa B (NFțB) is also discussed in terms of the disturbed redox balance (illustrated by the altered ratio of the activity of an array of antioxidant enzymes) and altered proapoptotic/proplastic signalling, since it regulates transcription of a wide array of genes (like Bcl-2, NCAM). Such cellular conditions, provoked by CPSI, are also shown to affect susceptibility to mitochondrially triggered apoptosis (illustrated by redistribution of Bcl family members and DNA fragmentation, more prominent in the PFC) and to simultaneously affect expression of main neural plasticity protein, polysialylated NCAM (PSA-NCAM). In summary, we present novel causal connection between the redox imbalance in the CNS, altered signalling via JNK and CDK kinases, GR phosphorylation/transactivity and NFțB transactivity, as well as their cellular imbalance, the parameters which all together yield inadequate CNS and systemic stress response.", journal = "Horizons in Neuroscience Research", booktitle = "Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats", volume = "5", pages = "97-126", url = "https://hdl.handle.net/21.15107/rcub_vinar_12040" }
Radojčić, M., Adžić, M., Nićiforović, A., Đorđević, J., Đorđević, A., Demonacos, C.,& Krstić-Demonacos, M.. (2011). Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats. in Horizons in Neuroscience Research, 5, 97-126. https://hdl.handle.net/21.15107/rcub_vinar_12040
Radojčić M, Adžić M, Nićiforović A, Đorđević J, Đorđević A, Demonacos C, Krstić-Demonacos M. Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats. in Horizons in Neuroscience Research. 2011;5:97-126. https://hdl.handle.net/21.15107/rcub_vinar_12040 .
Radojčić, Marija, Adžić, Miroslav, Nićiforović, Ana, Đorđević, Jelena, Đorđević, Ana, Demonacos, Constantinos, Krstić-Demonacos, Marija, "Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats" in Horizons in Neuroscience Research, 5 (2011):97-126, https://hdl.handle.net/21.15107/rcub_vinar_12040 .