title: Immunohistochemical changes induced by repeated footshock stress: revelations of gender-based differences.
abstract: As a growing literature has proven, adverse experiences, particularly when severe and persistent, play a pivotal role in the development of neuronal dysfunctions and psychopathology. In the present study, the neurochemical changes induced by acute and repeated footshock exposure were investigated at the molecular and cellular level, using c-fos and phospho-ERK1/2 immunoreactivity and gene expression arrays. Marked gender-related differences were found following both acute and prolonged footshock exposure. Acute aversive conditioning resulted in significant immunohistochemical changes that might be critically involved in the modulation of fear-related responses, especially in males. Prolonged footshock exposure, on the contrary, was associated with sustained hypothalamic-pituitary-adrenal axis hyperactivity, differential gender-related patterns of cortical-limbic activity, and abnormal neuronal plasticity, especially in medial prefrontocortical regions. These data may provide additional insights into the understanding of the neural circuits underlying the effects of acute and repeated footshock exposure as well as clarify some of the mechanisms involved in the development of stress-related neuronal abnormalities.
authors.affiliation: Department of Psychiatry, Division of Biological Psychiatry, Academic Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Trentani
authors.forename: S D
authors.initials: SD
authors.lastname: Kuipers
authors.forename: G J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: J
authors.initials: J
authors.lastname: Beekman
authors.forename: G J
authors.initials: GJ
authors.lastname: ter Horst
authors.forename: J A
authors.initials: JA
authors.lastname: den Boer
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects; D005239:Fear / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007150:Immunohistochemistry; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D020928:Mitogen-Activated Protein Kinases