Vasopressinergic modulation of stress responses in the central amygdala of the Roman high-avoidance and low-avoidance rat

The central nucleus of the amygdala (CEA) is selectively involved in the passive component of the behavioral (immobility) and the accompanying parasympathetic response during conditioned, stressful environmental challenges. Vasopressinergic mechanisms in the brain seem to play a role in these stress responses. The effects of the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) on modulating CEA activity during conditioned stress of inescapable footshock were studied in male Roman high-avoidance (RHA/Verh) and low-avoidance (RLA/Verh) rats, psychogenetically selected on the basis of shuttle-box acquisition behavior. In RLA/Verh rats, the cardiac and behavioral responses to the conditioned emotional stressor were bradycardia and immobility, suggesting an important role for the CEA in these rats. The RHA/Verh rats, however, failed to show any change in heart rate or immobility in response to a conditioned stress situation. The low dose of AVP (20 pg) in the CEA of conscious RLA/Verh rats caused an enhancement of the stress-induced bradycardiac and immobility response. However, the high dose of AVP (2 ng) and OXT (200 pg) attenuated the bradycardiac and immobility responses in the RLA/Verh rats. Infusion of AVP and OXT in the RHA/Verh rats failed to induce any change in heart rate nr immobility. Binding studies revealed that the AVP receptor selectively binds AVP with high affinity. In contrast, the OXT receptor recognizes both AVP and OXT with a similar (but lower) affinity. This suggests that the behavioral and autonomic responses of the high dose of AVP may be caused by OXT receptor stimulation. In conclusion, on the basis of the present results one may hypothesize that CEA differences in AVP and OXT innervation and/or receptor densities may contribute to the differences in coping strategy found in these animals.

CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy

SummaryObjectiveThe role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA.DesignOA was induced in 10 weeks old male wild type (WT), Ccl2−/− and Ccr2−/− mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naïve and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance.ResultsAbsence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average chondropathy score was observed in both Ccl2−/− and Ccr2−/− mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2−/− mice. Pain-related behaviour in Ccl2−/− and Ccr2−/− mice post DMM was delayed in onset.ConclusionThe CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage

Energy Localization in the Peyrard-Bishop DNA model

We study energy localization on the oscillator-chain proposed by Peyrard and Bishop to model the DNA. We search numerically for conditions with initial energy in a small subgroup of consecutive oscillators of a finite chain and such that the oscillation amplitude is small outside this subgroup for a long timescale. We use a localization criterion based on the information entropy and we verify numerically that such localized excitations exist when the nonlinear dynamics of the subgroup oscillates with a frequency inside the reactive band of the linear chain. We predict a mimium value for the Morse parameter $(\mu >2.25)$ (the only parameter of our normalized model), in agreement with the numerical calculations (an estimate for the biological value is $\mu =6.3$). For supercritical masses, we use canonical perturbation theory to expand the frequencies of the subgroup and we calculate an energy threshold in agreement with the numerical calculations