Production, regulation and role of nitric oxide in glial cells.

In neuropathological conditions such as Alzheimer's disease, Parkinson's disease, AIDS dementia complex and multiple selerosis, activation of microglial cells and astroglial cells is evident. Under these neuropathological conditions cellular damage in the brain is considered to arise indirectly from cytotoxic substances produced by activated glial cells. One of these toxins is NO which has been demonstrated to be produced during several neuropathological conditions. High NO levels are produced by glial cells and exert neurotoxic effects. Astroglial cells and microglial cells communicate in various ways to reduce NO production by microglial cells which is essential to maintain homeostasis in the brain. The production of TGFβ by glial cells and its activation by astrocyte-derived tPA represents one mechanism by which astroglia limit NO production in the brain

Strategic Partnerships: MAVAs approach to scaling up conservation impact

The world faces big challenges for nature, society, and the economy. The coming decade is the time we have to find solutions that put us on the right path towards a better future. Today's interconnected and interdependent world requires people and organisations from multiple backgrounds and interests to find a better way to work together on shared objectives in order to find these solutions.MAVA Foundation, whose vision is to create a world where biodiversity thrives and the economy supports human prosperity and a healthy planet, had to step up and walk the talk. In 2016, MAVA embarked with its partners on a transformative journey, aimed at ambitious and sustainable impact through meaningful collaboration.We share our learnings on this approach in a publication collectively written by MAVA and FOS Europe staff, with inputs from MAVA partners

Conservation Learning Initiative: Learn from evidence. Improve Conservation

The conservation community needs smarter and more successful actions to improve the impact of its work. For example, it is not always clear how to create training programmes that improve performance in a lasting way, or what the ingredients of a successful conservation partnership are, or how donors can set up funding so that grantees can work in a strategic and sustainable way.One way of designing successful, effective actions is through using insights from evidence-based learning. Recent years have seen significant steps forward in developing concepts for defining and using evidence in conservation. In late 2021, the MAVA Foundation, Foundations of Success (FOS), and Conservation Evidence joined forces in an initiative to build further on this work.Combining the strengths of their approaches with MAVA's treasure of nearly 30 years of conservation data, they set out to formulate assumptions and collect evidence to answer key learning questions. The results of this joint work are now available on the Conservation Learning Initiative website (https://conservation-learning.org/) and in a consolidated report.The website and report present:A practical 5-step approach for evidence-based learning in conservation, designed for combining different sources of evidence, dealing with differences in reliability and relevance, and drawing conclusions.Valuable insights based on data regarding four widely used conservation strategies: capacity-building, forming partnerships and alliances, providing flexible funding, and research and monitoring.The lessons learned will help conservationists fine-tune their work or investment to increase their conservation impact. By applying the approach on their own data, they can learn from evidence to make better decisions and improve strategies over time

The future is now: early life events preset adult behaviour

To consider the evidence that human and animal behaviours are epigenetically programmed by lifetime experiences. Extensive PubMed searches were carried out to gain a broad view of the topic, in particular from the perspective of human psychopathologies such as mood and anxiety disorders. The selected literature cited is complemented by previously unpublished data from the authors' laboratories. Evidence that physiological and behavioural functions are particularly sensitive to the programming effects of environmental factors such as stress and nutrition during early life, and perhaps at later stages of life, is reviewed and extended. Definition of stimulus- and function-specific critical periods of programmability together with deeper understanding of the molecular basis of epigenetic regulation will deliver greater appreciation of the full potential of the brain's plasticity while providing evidence-based social, psychological and pharmacological interventions to promote lifetime well-being.Work reported from the authors' laboratories was supported by European Union-funded projects CRESCENDO (FP6 Integrated Project 018652 to OFXA and DS) and SWITCHBOX (FP 7 Integrated Project 259772 to OFXA and NS). OFXA and DS were supported by the Max Planck Institute of Psychiatry and thank Professor Florian Holsboer for encouraging this work

Involvement of Noradrenergic Transmission in the PVN on CREB Activation, TORC1 Levels, and Pituitary-Adrenal Axis Activity during Morphine Withdrawal

Experimental and clinical findings have shown that administration of adrenoceptor antagonists alleviated different aspects of drug withdrawal and dependence. The present study tested the hypothesis that changes in CREB activation and phosphorylated TORC1 levels in the hypothalamic paraventricular nucleus (PVN) after naloxone-precipitated morphine withdrawal as well as the HPA axis activity arises from α1- and/or β-adrenoceptor activation. The effects of morphine dependence and withdrawal on CREB phosphorylation (pCREB), phosphorylated TORC1 (pTORC1), and HPA axis response were measured by Western-blot, immunohistochemistry and radioimmunoassay in rats pretreated with prazosin (α1-adrenoceptor antagonist) or propranolol (β-adrenoceptor antagonist). In addition, the effects of morphine withdrawal on MHPG (the main NA metabolite at the central nervous system) and NA content and turnover were evaluated by HPLC. We found an increase in MHPG and NA turnover in morphine-withdrawn rats, which were accompanied by increased pCREB immunoreactivity and plasma corticosterone concentrations. Levels of the inactive form of TORC1 (pTORC1) were decreased during withdrawal. Prazosin but not propranolol blocked the rise in pCREB level and the decrease in pTORC1 immunoreactivity. In addition, the HPA axis response to morphine withdrawal was attenuated in prazosin-pretreated rats. Present results suggest that, during acute morphine withdrawal, NA may control the HPA axis activity through CREB activation at the PVN level. We concluded that the combined increase in CREB phosphorylation and decrease in pTORC1 levels might represent, in part, two of the mechanisms of CREB activation at the PVN during morphine withdrawal