Proteinase-activated receptor 2 is involved in the behavioural changes associated with sickness behaviour

Proteinase-activated receptor-2 (PAR2) is widely expressed in the CNS but whether it plays a key role in inflammation-related behavioural changes remains unknown. Hence, in the present study we have examined whether PAR2 contributes to behaviour associated with systemic inflammation using PAR2 transgenic mice. The onset of sickness behaviour was delayed and the recovery accelerated in PAR2-/- mice in the LPS-induced model of sickness behaviour. In contrast, PAR2 does not contribute to behaviour under normal conditions. In conclusion, these data suggest that PAR2 does not contribute to behaviour in the normal healthy brain but it plays a role in inflammation-related behavioural changes

Evaluation of the Total Antioxidant Capacity of Bitter and Sweet Varieties of Ferula assa-foetida and Bunium persicum

Background: Due to low information about total antioxidant capacity of three species of plants native to Ilam province which are used in the ethnobotanical knowledge of this region, This study was drafting to evaluation the antioxidant ability of bitter and sweet varieties of Ferula assa-foetida and Bunium persicum with therapeutic potential on gynecological diseases.Methods: The methanolic extracts of two different variants of F. assa-foetida and B. persicum gum-resin were prepared and then antioxidant effects were evaluated by ferric reducing-antioxidant power assay.Results: Our results showed that methanolic extracts of B. persicum gum-resin could significantly revealed antioxidant effect in comparison to two different variants of F. assa-foetida (P<0.05). While antioxidant capacity between bitter and sweet varieties of F. assa-foetida were not statistically significant.Conclusion: Our results showed that both B. persicum and the bitter and sweet varieties of F. assa-foetida native to Ilam province, located in west of Iran, could have medicinal therapeutic effects relatively through direct oxidation prevention

Protease-activated receptor 2 activation induces behavioural changes associated with depression-like behaviour through microglial-independent modulation of inflammatory cytokines

Rationale: Major depressive disorder (MDD) is a leading cause of disability worldwide but currently prescribed treatments do not adequately ameliorate the disorder in a significant portion of patients. Hence, a better appreciation of its aetiology may lead to the development of novel therapies. Objectives: In the present study, we have built on our previous findings indicating a role for protease-activated receptor-2 (PAR2) in sickness behaviour to determine whether the PAR2 activator, AC264613, induces behavioural changes similar to those observed in depression-like behaviour. Methods: AC264613-induced behavioural changes were examined using the open field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), and novel object recognition test (NOR). Whole-cell patch clamping was used to investigate the effects of PAR2 activation in the lateral habenula with peripheral and central cytokine levels determined using ELISA and quantitative PCR. Results: Using a blood–brain barrier (BBB) permeable PAR2 activator, we reveal that AC-264613 (AC) injection leads to reduced locomotor activity and sucrose preference in mice but is without effect in anxiety and memory-related tasks. In addition, we show that AC injection leads to elevated blood sera IL-6 levels and altered cytokine mRNA expression within the brain. However, neither microglia nor peripheral lymphocytes are the source of these altered cytokine profiles. Conclusions: These data reveal that PAR2 activation results in behavioural changes often associated with depression-like behaviour and an inflammatory profile that resembles that seen in patients with MDD and therefore PAR2 may be a target for novel antidepressant therapies

Role of proteinase-activated receptor-2 in central mediated behaviour

Proteinase-activated receptors (PARs) are a family of novel G protein-coupled receptors, which are widely expressed in the brain. It has been recently shown that PAR2 activation indirectly modulates hippocampal neuronal excitability and synaptic transmission in vitro, and treatment with the PAR2 agonist SLIGRL-NH2 induced deficits in tests of motivational learning in rats. Hence, in this study we have investigated whether PAR2 deletion affects mouse behaviour in tests of learning and emotional behaviours under physiological and pathological conditions. Deletion of PAR2 had no effect on locomotor activity in the open field test. Heterozygous males appeared more anxious in the open field test but knockout females exhibited less anxiety in the elevated plus maze. PAR2 deletion had no effect on spatial reference memory in the Morris water maze but reduced mean percent alternation to chance level in the T-maze continuous alternation test and produced deficits in the male mice in the novel object recognition test. Deletion of PAR2 did not affect general startle reactivity and sensorimotor gating but it decreased the startle response at the highest stimuli in females. In a sickness behaviour model, deletion of PAR2 delayed induction of anhedonia as measured in the sucrose preference test after injection of lipopolysaccharide. It also induced a more rapid recovery from other symptoms of sickness behaviour as shown by increased locomotor activity 24 and 48 h post injection, increased body weight at 48 and 72 h post injection, increased food intake during the second day post injection and reduced anxiety-like behaviour 24 h post injection. The novel PAR2 agonist AC-264613 penetrated into mouse brain. AC-264613 had no effects on locomotor activity and anxiety-like behaviour but showed a tendency to induce anhedonia. In conclusion, these data indicate that proteinase-activated receptor-2 may be involved in mouse behaviour under normal and pathological conditions.Proteinase-activated receptors (PARs) are a family of novel G protein-coupled receptors, which are widely expressed in the brain. It has been recently shown that PAR2 activation indirectly modulates hippocampal neuronal excitability and synaptic transmission in vitro, and treatment with the PAR2 agonist SLIGRL-NH2 induced deficits in tests of motivational learning in rats. Hence, in this study we have investigated whether PAR2 deletion affects mouse behaviour in tests of learning and emotional behaviours under physiological and pathological conditions. Deletion of PAR2 had no effect on locomotor activity in the open field test. Heterozygous males appeared more anxious in the open field test but knockout females exhibited less anxiety in the elevated plus maze. PAR2 deletion had no effect on spatial reference memory in the Morris water maze but reduced mean percent alternation to chance level in the T-maze continuous alternation test and produced deficits in the male mice in the novel object recognition test. Deletion of PAR2 did not affect general startle reactivity and sensorimotor gating but it decreased the startle response at the highest stimuli in females. In a sickness behaviour model, deletion of PAR2 delayed induction of anhedonia as measured in the sucrose preference test after injection of lipopolysaccharide. It also induced a more rapid recovery from other symptoms of sickness behaviour as shown by increased locomotor activity 24 and 48 h post injection, increased body weight at 48 and 72 h post injection, increased food intake during the second day post injection and reduced anxiety-like behaviour 24 h post injection. The novel PAR2 agonist AC-264613 penetrated into mouse brain. AC-264613 had no effects on locomotor activity and anxiety-like behaviour but showed a tendency to induce anhedonia. In conclusion, these data indicate that proteinase-activated receptor-2 may be involved in mouse behaviour under normal and pathological conditions