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Maternal immune activation (MIA) disrupts the central innate immune system during a critical neurodevelopmental period. Microglia are primary innate immune cells in the brain although their direct influence on the MIA phenotype is largely unknown. Here we show that MIA alters microglial gene expression with upregulation of cellular protrusion/neuritogenic pathways, concurrently causing repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons in the prefrontal cortex of mice. MIA increases plastic dendritic spines of the intrinsically bursting neurons and their interaction with hyper-ramified microglia. Treating MIA offspring by colony stimulating factor 1 receptor inhibitors induces depletion and repopulation of microglia, and corrects protein expression of the newly identified MIA-associated neuritogenic molecules in microglia, which coalesces with correction of MIA-associated synaptic, neurophysiological, and behavioral abnormalities. Our study demonstrates that maternal immune insults perturb microglial phenotypes and influence neuronal functions throughout adulthood, and reveals a potent effect of colony stimulating factor 1 receptor inhibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions.

The role of Arc in synaptic plasticity and memory consolidation has been investigated for many years with recent evidence that defects in the expression or activity of this immediate-early gene may also contribute to the pathophysiology of brain disorders including schizophrenia and fragile X syndrome. These results bring forward the concept that reversing Arc abnormalities could provide an avenue to improve cognitive or neurological impairments in different disease contexts, but how to achieve this therapeutic objective has remained elusive. Here, we present results from a chemogenomic screen that probed a mechanistically diverse library of small molecules for modulators of BDNF-induced Arc expression in primary cortical neurons. This effort identified compounds with a range of influences on Arc, including promoting its acetylation—a previously uncharacterized post-translational modification of this protein. Together, our data provide insights into the control of Arc that could be targeted to harness neuroplasticity for clinical applications., The activity-regulated cytoskeleton-associated protein (Arc) has been implicated in synaptic plasticity and memory consolidation. Here the authors show that Arc acetylation regulates its stability and identify small molecules that modulate Arc expression.

Background: This paper presents lessons learnt from a Jisc-funded research project that developed and implemented an information communication technology tool enabling staff to understand the environmental impact of their activities and support sustainable procurement across De Montfort University (Leicester, UK). Results: An environmentally extended input–output calculation approach was adopted to calculate the emissions and a ‘dashboard style’ approach was used to present the information. While the tool was developed successfully, its institutional impact was limited by numerous barriers. Conclusion: These challenges provided several key learning points: cost remains the main priority in procurement teams much higher than environmental aspects; committed ‘champions’ are key to organizational change; and information communication technology carbon/sustainability tools need to be an integral part of an organization’s existing procurement systems.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Better understanding of the factors influencing how people use energy in public buildings can help deliver more effective CO2 reduction strategies. This paper describes the institutional, social and individual behavioural effects of communication campaigns in over 500 public buildings in 11 European cities. These campaigns involved engaging with staff to reduce energy use through feedback services based on information from sub hourly meter readings. A summative evaluation was conducted to understand impacts of different information provision in these cities. Qualitative data were gathered through a set of interviews with 40 building professionals at the central or building level. These interviews identified differences in how the energy efficiency communication-based campaigns were implemented at each site and elicited factors to explain how users’ perceptions and understanding changed as a result of the interventions. The evaluation framework helped to identify not only improvements in the delivery of communication-based campaigns, but also the communication factors that impacted on individual behaviour change. The research highlighted the influence of institutional and social effects on individual beliefs and norms. To achieve more effective change in attitudes to reduce use, energy feedback needs to be supported with engagement activities, such as energy coaches, campaigns, and interactive online fora.