LongTerm Consequences of immobilization stress
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1
Sultan Moulay Slimane University, Faculty of Sciences & Techniques, Life Sciences, Morocco
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2
Université de Tours, INRA, CNRS, France
Adult mammals secrete glucocorticoids (GCs) in a circadian fashion and in response to stressful stimuli. Indeed, exposure
of animals to stressful conditions induces a wide range of behavioural and physiologic responses (Chigr et al., 2001, 2009; Charrier et al., 2006), the best characterized being the activation of the hypothalamic-pituitary-adrenal (HPA) manifested by the release of adrenocorticotropin hormone: ACTH and GCs into the blood) (Kvetnansky et al., 1995; Dal-Zotto et al., 2002). The surge observed in ACTH and GCs secretion depends on the stress paradigm used and at lesser degree its duration. It represents the adaptive response to counterattack the negative effects of stress. After the termination of exposure to stressors, the HPA hormones need from 1 to several hours (>8 hr). This represents an evidence for lasting changes in resting activity of the HPA axis after a single exposure to stress. Interestingly and from a physiological point, a strong stress as immobilization, induces anorexia-like effect notably, 24 hr post stress. This suggests greatly that GCs may affect the central regulation of food intake (FI), probably by interacting with factors involved in this regulation. Therefore, we decided to study the long term effects of a single exposure to immobilization (1 hour) on the expression of anorexigenic and orexigenic factors in different brain structures, principally those related to food intake control. In order to investigate the involvement of the signaling of these factors in the food control, notably in the context of food intake alterations (anorexia caused by stress), we analysed the hypothalamic and dorso vagal complex (DVC) expression of neuropeptide Y (NPY), Agouti related peptide (AgRP), brain-derived neurotrophic factor (BDNF), Pro-opiomelanocortin (POMC) and cocaine amphetamine related transcript (CART) mRNAs. 5 rat groups were dedicated to these investigations. The rats of four groups were immobilized for 1 hour, and were then sacrificed just after the end of stress session (group 1), 24 hours after (Group 2), 48 hours after (group 3) or 72 hours after (group 4). The unstressed rats constitute the control group. The mRNA extracts were processed by RT-PCR technique. Firstly, we characterizd the effects of 1 hour immobilization stress on food intake behaviour and found that body weight as well as food intake are negatively affected. This is well illustrated 24 hours hours after the cessation of stress session. Both body weight and food intake tend to increase at 48 and 72 hours after but did not reach the positive control evolution. Concerning, the anorexigenic factors investigated, we showed for BDNF, that anorexia-inducing immobilization stress (IS) triggers different BDNF recruitment patterns between DVC and hypothalamus. While there is no significant evolution of BDNF mRNA in hypothalamus, exons 1 mRNA and 3 mRNA was down regulated respectively 72 and 24 hours post stress whereas exon 5 mRNA was upregulated 3 hours post stress. A tendency in the increase of exons mRNA between 3 and 72 hours post stress was observed but still not significant. Furthermore, we showed, by using RTPCR that the mRNAs of the two other anorexigenic peptides display significant increases in stressed rats compared to controls, although with differential peaks. In hypothalamus, POMC and CART transcript upregulation is observed at the end of IS and up to 24 hours. It persists until 48-72h after IS for CART only. In the DVC, expression of the two transcripts peaks significantly at 24h post stress and decline afterwards; POMC mRNA reach then the equivalent levels observed in controls, whereas CART mRNA is downregulated after 48h post stress. When the orexigenic peptides were considered, NPY and AgRP mRNAs show a gradual increase just after the end of the immobilization in the hypothalamus of stressed rats. The up regulation is significant only at 24 hours after stress for AgRP but remains significantly higher than in controls for NPY. In DVC, the transcripts of the two factors show general similar post stress evolution. A significant increase jut after the end of immobilization of rats which persists up to 24 hours after is firstly noticed. The levels tend then to reach the basal levels although, they still slightly but significantly higher up to 72 hours after stress for mRNA NPY. The comparison between the expression profiles of anorexigenic peptides (pricipally POMC and CART) and the two orexigenic peptides investigated (AgRP and NPY) shows the presence of a parallelism between that of POMC and AgRP and that of CART and NPY when each brain region (hypothalamus and DVC) is considered separately. It seems that any surge in the expression of each anorexigenic factor stimulates the expression of those of corresponding and appropriated orexigenic one. These last reactions from orexigenic peptides tend to attenuate the anorexigenic effects of CART and POMC and by consequent to abolish the anorexia state generated by stress. The persistence of alteration of the expression of anorexigenic and orexigenic factors during the post-stress period could be highly related to the slow recovery of the HPA axis in IS and points to stress-induced plasticity in both nervous centers of food intake regulation. This is corroborated by the peak of Gcs and ACTH just after the cessation of immobilization and their long lasting many hours after compared to control rats where basal circadian rythms of Gcs are maintained. Indeed, the speed of the recovery of the HPA axis depends on the stress paradigm, its intensity and its duration as well as the previous experience (Marti et al., 1994). In any case, it seems that Gcs may regulate directly or indirectly, orexigenic and anorexigenic factors expression to reach a homeostatic state. In summary, this study shows that correlations exist between various physiological responses measured just after the termination of the exposure to the stressor but are very proeminent in the post stress period (Marquez et al., 2002). Taken together these findings indicate that the heterogeneous GCs action have to be assimilated into a physiological role of food intake regulation (Morton et al., 2006).
Acknowledgements
Acknowledgment: GDRI Neuro (CNRS-CNRST, France – Maroc), PICS CNRS-CNRST (France Maroc), Université Aix Marseille 3, Neuromed FP7.
References
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Keywords:
Stress, Psychological,
Hypothalamo-Hypophyseal System,
brainstem,
orexigenic peptides,
anorexigenic action,
Glucocorticoids
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Najimi
M,
Chigr
F and
Moyse
E
(2013). LongTerm Consequences of immobilization stress.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00054
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Received:
31 Mar 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Prof. Mohamed Najimi, Sultan Moulay Slimane University, Faculty of Sciences & Techniques, Life Sciences, Beni Mellal, Morocco, mnajimi1@fstbm.ac.ma