title: Chronic stress induces prolonged suppression of the P2X7 receptor within multiple regions of the hippocampus: a cumulative threshold spectra analysis.
abstract: A number of studies have identified that mutations in the P2X7 receptor occur with a significantly higher incidence in individuals with major depression. Consistent with these findings, a number of preclinical studies have identified that mice in which the P2X7 receptor has been deleted exhibit a higher level of resilience-like behaviour to acutely aversive situations. At present, however, no studies have examined changes in P2X7 receptor expression in otherwise healthy animals exposed to persistently stressful situations. This is significant as several lines of evidence have demonstrated that it is exposure to persistently aversive, rather than acutely aversive, situations that is associated with the emergence of mood disturbance. Accordingly, the objective of the current study was to examine whether chronic exposure to restraint stress was associated with alterations in the expression of P2X7 within the hippocampal formation. The study involved three principal groups: acute stress (1 session), chronic stress (21 sessions, 1 per day) and a chronic stress with recovery group (21 sessions, 1 per day followed by 7days of no stress) and appropriate control groups. The results of the analysis indicate that all forms of stress, regardless of the duration, provoked a reduction in P2X7 receptor expression. Comparative analysis on normalised data indicated that the magnitude of the P2X7 reduction was significantly greater in the chronic stress relative to the acute stress group. We additionally found that there was a gradual rebound in P2X7 expression, in two of nine regions examined, in animals that were allowed to recover for 7days following the final stress session. Collectively, these findings provide the first evidence that exposure to chronic restraint stress produces a pronounced and relatively persistent suppression of the P2X7 receptor within the hippocampus.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Ratchaniporn
authors.initials: R
authors.lastname: Kongsui
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Beynon
authors.affiliation: School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Johnson
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Jack
authors.initials: J
authors.lastname: Mayhew
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kuter
authors.affiliation: Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Centre for Translational Neuroscience and Mental Health Research, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia. Electronic address: rohan.walker@newcastle.edu.au.
authors.forename: Frederick Rohan
authors.initials: FR
authors.lastname: Walker
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7
keywords: ATP; Hippocampus; P2X7; Purines; Rat; Stress