Leptin prevents aberrant targeting of tau to hippocampal synapses via PI 3 kinase driven inhibition of GSK3β

Amyloid-β (Aβ) and hyper-phosphorylated tau are key hallmarks of Alzheimer's disease (AD), with an accumulation of both proteins linked to hippocampal synaptic dysfunction. Recent evidence indicates that Aβ drives mis-localisation of tau from axons to synapses, resulting in AMPA receptor (AMPAR) internalisation and impaired excitatory synaptic function. These tau-driven synaptic impairments are thought to underlie the cognitive deficits in AD. Consequently, limiting the synapto-toxic effects of tau may prevent AD-related cognitive deficits. Increasing evidence links leptin dysfunction with higher AD risk, and numerous studies have identified neuroprotective properties of leptin in AD models of Aβ-induced toxicity. However, it is unclear if leptin protects against tau-related synaptic dysfunction. Here we show that Aβ 1-42 significantly increases dendritic and synaptic levels of tau and p-tau in hippocampal neurons, and these effects were blocked by leptin. In accordance with GSK-3β being involved in tau phosphorylation, the protective effects of leptin involve PI 3-kinase (PI3K) activation and inhibition of GSK-3β. Aβ 1-42-driven synaptic targeting of tau was associated with the removal of GluA1-containing AMPARs from synapses, which was also inhibited by leptin-driven inhibition of GSK-3β. Direct application of oligomeric tau to hippocampal neurons caused internalisation of GluA1-containing AMPARs and this effect was blocked by prior application of leptin. Similarly, leptin prevented the ability of tau to block induction of activity-dependent long-term potentiation (LTP) at hippocampal SC-CA1 synapses. These findings increase our understanding of the neuroprotective actions of leptin in the early pre-clinical stages of AD and further validate the leptin system as a therapeutic target in AD. (Figure presented.)</p

Sport fan attitudes on alcohol:Insights from a survey of football supporters in Scotland and England

Availability of alcohol at football matches in the UK is much debated and subject to multiple restrictions, yet there is little understanding of supporters’ attitudes. A cross-sectional survey of football supporters in Scotland and England (n  =  1750) was conducted April–June 2019. Most supporters viewed drinking at matches as acceptable (74.4%) and thought alcohol should be available at grounds (76.0%); around two-fifths thought most supporters consumed alcohol before matches (44.1%); but only a quarter (26.6%) thought disorder at matches was due to alcohol. Attitudes varied by supporter characteristics: supporters who were younger, in England, or more regular match-goers were more favourable towards alcohol consumption and availability at matches. We conclude that alcohol regulations in some nations and sports – where restrictions are based on historical disorder – may no longer be appropriate

Developing a health inequalities approach for mental health social work

YesDespite increasing evidence of the impact of health inequalities on mental health (Pickett and Wilkinson, 2015) there is only limited recognition of the potential role for mental health social work in addressing ‘upstream’ as well as ‘downstream’ challenges of poverty, disadvantage and oppression affecting many people experiencing mental health difficulties. This paper presents some of the current evidence concerning mental health inequalities and the opportunities for mental health social workers to promote wellbeing. A theme throughout the paper is the need to avoid the many examples of dichotomous thinking that frequently characterise thinking about mental health and mental health practice. Additionally the limitations of an individualised recovery discourse are acknowledged. Drawing on Krieger’s (2011) ecosocial model, the social determinants of mental health are considered and the concept of embodiment is examined for its contribution to a more nuanced understanding of the relationship between inequality and health. Finally, the paper offers a version of mental health social work that ‘faces both ways’, involving issues at both the individual and the wider societal level. This includes developing and extending partnerships with service users and carers and with other professional and agencies

Stakeholder views of current laws surrounding alcohol at UK football matches:Is it a case of using a “sledgehammer to crack a nut”?

Background: In 2021, a fan-led review of football governance in England recommended that legislation surrounding alcohol and football be reviewed to determine whether it is still fit for purpose, the first such review since the mid-1980s. Restricting football fans’ alcohol consumption has been debated in the UK for over 40 years. However, more research is needed into the current attitudes of fans and influential stakeholders on this matter. Methods: Focus groups with football supporters (n=79) and semi-structured interviews (n=15) with key organisational stakeholders were conducted between November 2019 and February 2021. Focus groups included fans who regularly attended matches and supported various teams from professional leagues in Scotland and England, casual fans who usually watched games at home or in bars, and fans who followed the Scotland and England national teams. Stakeholders were selected to represent organisations likely to be instrumental in any regulatory change, such as the UK and Scottish Governments, Police, football supporters’ groups and safety organisations. Results: The current law does not allow for alcohol to be consumed within view of the pitch. Participants from England suggested this could be changed. While in Scotland, where the legislation only allows alcohol to be sold in hospitality, most participants were in favour of allowing the general sale of alcohol at football stadia via a pilot scheme. The reasons for these changes included: reducing unhealthy drinking behaviours; minimising the health and safety risk of fans arriving at the stadium just before kick-off; and a potential increase in much needed revenue for clubs. Conclusion: Our data suggests an evidence-based review of current laws regarding alcohol and football may be appropriate. However, any discussion regarding changes to the law regarding alcohol at football stadia, including potential pilot schemes, should be evaluated and monitored in terms of both financial impact and the impact on public health and safety

Sport Fan Attitudes on Alcohol: Insights from a Survey of Football Supporters in Scotland and England

Availability of alcohol at football matches in the UK is much debated and subject to multiple restrictions, yet there is little understanding of supporters’ attitudes. A cross-sectional survey of football supporters in Scotland and England (n  =  1750) was conducted April–June 2019. Most supporters viewed drinking at matches as acceptable (74.4%) and thought alcohol should be available at grounds (76.0%); around two-fifths thought most supporters consumed alcohol before matches (44.1%); but only a quarter (26.6%) thought disorder at matches was due to alcohol. Attitudes varied by supporter characteristics: supporters who were younger, in England, or more regular match-goers were more favourable towards alcohol consumption and availability at matches. We conclude that alcohol regulations in some nations and sports – where restrictions are based on historical disorder – may no longer be appropriate

No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex

Continuous theta burst stimulation (cTBS) is thought to reduce cortical excitability and modulate functional connectivity, possibly by altering cortical inhibition at the site of stimulation. However, most evidence comes from the motor cortex and it remains unclear whether similar effects occur following stimulation over other brain regions. We assessed whether cTBS over left dorsolateral prefrontal cortex altered gamma aminobutyric acid (GABA) concentration, functional connectivity and brain dynamics at rest, and brain activation and memory performance during a working memory task. Seventeen healthy individuals participated in a randomised, sham-controlled, cross-over experiment. Before and after either real or sham cTBS, magnetic resonance spectroscopy was obtained at rest to measure GABA concentrations. Functional magnetic resonance imaging (fMRI) was also recorded at rest and during an n-back working memory task to measure functional connectivity, regional brain activity (low-frequency fluctuations), and task-related patterns of brain activity. We could not find evidence for changes in GABA concentration (P = 0.66, Bayes factor [BF10] = 0.07), resting-state functional connectivity (P(FWE) > 0.05), resting-state low-frequency fluctuations (P = 0.88, BF10 = 0.04), blood-oxygen level dependent activity during the n-back task (P(FWE) > 0.05), or working memory performance (P = 0.13, BF10 = 0.05) following real or sham cTBS. Our findings add to a growing body of literature suggesting the effects of cTBS are highly variable between individuals and question the notion that cTBS is a universal ‘inhibitory’ paradigm

GABA A Receptor α1 Subunit Deletion Prevents Developmental Changes of Inhibitory Synaptic Currents in Cerebellar Neurons

Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstrated previously in cerebellar neurons in rodents. We report that these kinetic changes in mice are determined primarily by developmental changes in GAB

Beings in their own right? Exploring Children and young people's sibling and twin relationships in the Minority World

This paper examines the contributions that the sociological study of sibship and twinship in the Minority World can make to childhood studies. It argues that, in providing one forum within which to explore children and young people's social relationships, we can add to our understanding of children and young people's interdependence and develop a more nuanced understanding of agency. As emergent subjects, children, young people and adults are in a process of ‘becoming’. However, this does not mean that they can ‘become’ anything they choose to. The notion of negotiated interdependence (Punch 2002) is useful in helping us to grasp the contingent nature of children and young people's agency