Edel Hughes

Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1

Aberrant activation of toll-like receptors (TLRs), key components of the innate immune system, has been proposed to underlie and exacerbate a range of central nervous system disorders. Increasing evidence supports a role for the endocannabinoid system in modulating inflammatory responses including those mediated by TLRs, and thus this system may provide an important treatment target for neuroinflammatory disorders. However, the effect of modulating endocannabinoid tone on TLR-induced neuroinflammation in vivo and associated behavioural changes is largely unknown. The present study examined the effect of inhibiting fatty acid amide hydrolyase (FAAH), the primary enzyme responsible for the metabolism of anandamide (AEA), in vivo on TLR4-induced neuroimmune and behavioural responses, and evaluated sites and mechanisms of action. Systemic administration of the FAAH inhibitor PF3845 increased levels of AEA, and related FAAH substrates N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA), in the frontal cortex and hippocampus of rats, an effect associated with an attenuation in the expression of pro- and anti-inflammatory cytokines and mediators measured 2hrs following systemic administration of the TLR4 agonist, lipopolysaccharide (LPS). These effects were mimicked by central i.c.v. administration of PF3845, but not systemic administration of the peripherally-restricted FAAH inhibitor URB937. Central antagonism of TRPV1 significantly attenuated the PF3845-induced decrease in IL-6 expression, effects not observed following antagonism of CB1, CB2, PPARα, PPARγ or GPR55. LPS-induced a robust sickness-like behavioural response and increased the expression of markers of glial activity and pro-inflammatory cytokines over 24hrs. Systemic administration of PF3845 modulated the TLR4-induced expression of neuroimmune mediators and anhedonia without altering acute sickness behaviour. Overall, these findings support an important role for FAAH substrates directly within the brain in the regulation of TLR4-associated neuroinflammation and highlight a role for TRPV1 in partially mediating these effects.

A democratic opening? The AKP and the Kurdish left

Abstract Since its foundation, militant democratic arguments have underpinned an enforced secularism in Turkey. The 2002 election of the AKP, described as a “moderate Islamist party”, has challenged Turkey’s secular identity. In the more than twelve years since the AKP has been in power, Turkey’s political landscape has experienced significant changes, with periods of extensive democratic reforms punctuated by regression in certain areas, notably freedom of expression and the right to protest. State repressive measures coupled with Recep Tayyip Erdoğan’s reluctance to exit the political stage have been the focus of much commentary and analysis. This article argues, however, that under AKP rule the Kurdish issue – critical to ensuring the normalization of politics and democratization in Turkey – has been brought in from the political cold and assesses the creation and role of the HDP (Halkların Demokratik Partisi), a Kurdish political party that is endeavoring to situate itself in the mainstream of Turkey’s political landscape. We posit that the HDP can be viewed as the offspring of this “democratic opening,” a project that was meant to ensure a radical transformation of the Kurdish issue in Turkey. Through analysing the historical trajectory of both AKP and HDP and the militant democratic arguments that led to their predecessors’ exclusion from the public sphere, this article engages with the key question of the extent to which the AKP’s treatment of the Kurdish issue has provided a vehicle for broader democratisation and facilitated a reconsideration of the Kurdish question in Turkey.

Identifying routes to remedy for violations of economic, social and cultural rights

ABSTRACT This article examines the status of economic, social and cultural (ESC) rights in Scotland and identifies routes to remedy for violations of these rights. ESC rights relate to areas such as housing, education, employment, standard of living and health. Violations of ESC rights impact on the most vulnerable in society. The mapping of rights conducted by the Scottish Human Rights Commission before the publication of the Getting It Right report revealed a legal deficit in the protection of ESC rights in Scotland. The evidence identified that protection mechanisms for socio-economic rights in Scotland are either insufficient or non-existent. This article builds on the evidence by exploring the legal nature of ESC rights: how they are currently protected in Scotland and how they are protected in other jurisdictions. It then examines the concept of a ‘remedy’ in international human rights law and proposes models for the better protection of ESC rights for potential future implementation in Scotland. This includes an examination of the risks and benefits in constitutionalising or legislating for ESC rights. This will be of interest to an international audience in terms of identifying justiciability mechanisms and models of constitutionalisation for ESC rights in different constitutional contexts, including Scotland.

The Secularism Debate and Turkey's Quest for European Union Membership

The potential accession of Turkey to the European Union is undoubtedly one of the Unions most contested prospective enlargements. Among the stated concerns are continuing problems surrounding Cyprus and Turkeys record in terms of fundamental human rights protections. The nature of the Turkish state and its current government, headed by the Islamic Refah Partisi, is also the subject of much discussion. This article traces the development of secularism in modern Turkey and outlines the effect that the Islamic revival is having on both Turkey and its attempts to join the ranks of the European Union.