PMID- 12753089 OWN - NLM STAT- MEDLINE DCOM- 20030724 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 85 IP - 5 DP - 2003 Jun TI - Molecular correlates of impaired prefrontal plasticity in response to chronic stress. PG - 1312-23 AB - Disturbed adaptations at the molecular and cellular levels following stress could represent compromised neural plasticity that contributes to the pathophysiology of stress-induced disorders. Evidence illustrates atrophy and cell death of stress-vulnerable neurones in the prefrontal cortex. Reduced plasticity may be realized through the destabilized function of selective proteins involved in organizing the neuronal skeleton and translating neurotrophic signals. To elucidate the mechanisms underlying these effects, rats were exposed to chronic footshock stress. Patterns of c-fos, phospho-extracellular-regulated protein kinases 1/2 (ERK1/2), calcineurin and phospho-cyclic-AMP response-element binding protein (CREB) expression were subsequently investigated. The results indicate chronic stress-induced impairments in prefrontal and cingulate signal transduction cascades underlying neuronal plasticity. The medial prefrontal cortex, demonstrated functional hyperactivity and dendritic phospho-ERK1/2 hyperphosphorylation, while reduced c-fos and calcineurin immunoreactivity occurred in the cingulate cortex. Significantly reduced phospho-CREB expression in both cortical regions, considering its implication in brain-derived neurotrophic factor (BDNF) transcription, suggests reduced synaptic plasticity. This data confirms the damaging effect of stress on cortical activity, on a molecular level. Due to the association of these markers in the regulation of BDNF signalling, these findings suggest a central role for intracellular neurotrophin transduction members in the pathways underlying cellular actions of stress in the brain. FAU - Kuipers, S D AU - Kuipers SD AD - Department of Psychiatry, Division of Biological Psychiatry, Academic Hospital Groningen, Groningen, The Netherlands. s.d.kuipers@acggn.azg.nl FAU - Trentani, A AU - Trentani A FAU - Den Boer, J A AU - Den Boer JA FAU - Ter Horst, G J AU - Ter Horst GJ LA - eng PT - Journal Article PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Proto-Oncogene Proteins c-fos) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.3.16 (Calcineurin) SB - IM MH - Animals MH - Body Weight MH - Calcineurin/metabolism MH - Chronic Disease MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Electroshock MH - Immunohistochemistry MH - Male MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/metabolism MH - *Neuronal Plasticity MH - Neurosecretory Systems/physiopathology MH - Phosphorylation MH - Prefrontal Cortex/cytology/*physiopathology MH - Proto-Oncogene Proteins c-fos/metabolism MH - Rats MH - Rats, Wistar MH - Stress, Physiological/*physiopathology EDAT- 2003/05/20 05:00 MHDA- 2003/07/25 05:00 CRDT- 2003/05/20 05:00 PHST- 2003/05/20 05:00 [pubmed] PHST- 2003/07/25 05:00 [medline] PHST- 2003/05/20 05:00 [entrez] AID - 1770 [pii] AID - 10.1046/j.1471-4159.2003.01770.x [doi] PST - ppublish SO - J Neurochem. 2003 Jun;85(5):1312-23. doi: 10.1046/j.1471-4159.2003.01770.x.