Congratulations to Dr. Deniz Karabag, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), and University of Cologne, Germany, on receiving the 2023 Mark Smith Award – now named the “Young Scientist Paper of the Year in Honour of Mark Smith”, for the article “Characterizing microglial senescence: Tau as a key player”.

This original study demonstrates that exposure of cultured microglia to tau enhances senescence, as measured phenotypically and neurochemically. In essence, this shifts the highlight from brain neurons to microglia as key partners in the induction and worsening of Alzheimer’s disease characteristics. The topic is critical for understanding mechanisms of age-dependent microglial alterations, and the results hold both fundamental and translational value. 

Congratulations to João Victor Cabral-Costa for the paper entitled “Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance”.  This paper presents a novel optogenetic tool that is likely to open new avenues to study the role of presynaptic potentiation in neuronal networks and their impact on behaviors, and is considered of wide interest because it provides specificity not afforded by pharmacological or electrical approaches to elicit synaptic potentiation with a high temporal and spatial precision.

The elegant and convincing study shows the involvement of mitochondrial calcium efflux by the sodium/calcium exchanger NCLX in astrocytic glucose metabolism and thus presenting a novel mechanism associating mitochondrial function with cognition. The authors prove their conclusions with a range of both pharmacological and genetic techniques, utilizing scRNA-seq data to guide the functional examination of NCLX in vivo. The targeting of NCLX deletion to either astrocytes or neurons represents an important advance, which produced intriguing differential effects on behavioral performance.

Congratulations to Dr. Md. Omar Faruk on the 2021 Mark A. Smith Award for the publication “Muscarinic signaling regulates voltage‐gated potassium channel KCNQ2 phosphorylation in the nucleus accumbens via protein kinase C for aversive learning”. The authors used advanced biochemical approaches such as targeted deletion of Kcnq2 in the nucleus accumbens (NAcc) to elucidate the molecular mechanisms of emotional behavior, including avoidance learning, mediated by the NAcc via muscarinic receptor (MR1) signaling, which was known to increase with foot shock and affect the functions of KCNQ2 potassium channels.

Dr. Faruk pursued a Bachelor and Master of Science at University of Dhaka in his home country, Bangladesh, where his work was already honored with a Dean’s Award for outstanding results in BS (Bachelor of Science) and a scholarship for excellent academic performance during the Master’s thesis. Dr. Faruk earned his PhD from Nagoya University, Graduate School of Medicine, Japan in Kozo Kaibuchi’s lab with a Monbukagakusho (MEXT) award from the Japanese Government. He now holds an assistance professorship at University of Dhaka.

Congratulations to Silvia Oldani who was first author of the paper entitled “SynaptoPAC, an optogenetic tool for induction of presynaptic plasticity”. This paper presents a novel optogenetic tool that is likely to open new avenues to study the role of presynaptic potentiation in neuronal networks and their impact on behaviors, and is considered of wide interest because it provides specificity not afforded by pharmacological or electrical approaches to elicit synaptic potentiation with a high temporal and spatial precision.

Silvia Oldani pursued her Master’s studies at the Università degli Studi di Milano in Milan from 2012 – 2014 where she graduated in Cell Molecular Biology with a thesis on neuronal network development at the University of Amsterdam in Netherlands under the supervision of Ruud Toonen in the laboratory of Prof. Dr. Matthijs Verhage. Silvia Oldani received a NeuroCure Excellence Cluster PhD fellowship from the Charité Berlin, where she pursued her PhD from 2015 under the supervision of Benjamin Rost and Prof. Dr. Dietmar Schmitz.

Congratulations to Wangqiu Huang, for the paper Metabolomics‐driven identification of adenosine deaminase as therapeutic target in a mouse model of Parkinson’s disease.
The paper uses a combination of interesting approaches to identify novel targets to diminish neurodegeneration in a
Parkinson disease (PD) mouse model, and is testing drugs that modulate the pathway to show they can approve neurochemical and behavioral outcomes in a mouse model of PD.

With the aim to identify novel inflammation-relevant targets associated with Parkinson’s disease (PD), the authors begin this study by performing a non-bias metabolomics approach in striatal tissue of mice exposed to LPS and MPTP (i.e. a “double-hit” approach). Their mass-spectrometry results, combined with metabolite-protein bioinformatics approaches, identified numerous metabolites of the purine metabolic pathway to be involved – in particular, decreases in adenosine levels. The authors proceeded to test their hypothesis by performing neurochemical, immunohistological and behavioral analysis in an acute MPTP-induced PD model using three treatments: ADA inhibition, adenosine receptor (AR) A2a inhibition, or a combination thereof. They found that while ADA inhibition alone improved dopamine depletion and was partially neuroprotective, combination treatments of ADA and AR A2a inhibitors were more efficacious in ameliorating MPTP effects on PD phenotypes.

Congratulations to Jonathan D. Lautz, “Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network”

Journal of Neurochemistry (2018) J Neurochem 146(5), 540-559.

Jonathan D. Lautz,  Emily A. Brown,  Alison A. Williams VanSchoiack,  Stephen E. P. Smith

DOI: 10.1111/jnc.14466

The study impressed by its comprehensive and thorough design and conduct and was judged as very innovative and future-leading. Lautz et al. utilized the quantitative multiplex co-immunoprecipitation platform they designed to analyze activity-dependent changes in PSD protein-protein interactions and showed that neurons respond differently to different types of glutamatergic inputs by modulating specific combinations of post-synaptic proteins associations.

Jonathan D. Lautz currently works as a postdoctoral fellow at Seattle Children’s Research Institute, Center for Integrative Brain Research under supervision of Dr. Stephen Smith

Congratulations to Scott Glen Canfield, for An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells
Journal of Neurochemistry (2017) J Neurochem 140(6):874-888.
Scott G. Canfield, Matthew J. Stebbins, Bethsymarie Soto Morales, Shusaku W. Asai, Gad D. Vatine, Clive N. Svendsen, Sean P. Palecek, Eric V. Shusta.
doi: 10.1111/jnc.13923

Read the Editorial Highlight for this article: https://doi.org/10.1111/jnc.13961
The article makes a very important contribution to the understanding of the blood-brain barrier (BBB). Canfield et al. used human-induced pluripotent stem cells (iPSCs) to derive endothelial cells, astrocytes, and neurons. Co-culture of those cells resulted in a human BBB model with excellent permeability characteristics, with transendothelial electrical resistances and passive permeabilities close to those found in vivo. This type of work is important because the integrity of the BBB is affected in several neurodegenerative disorders. Due to the intricate nature of the BBB it constitutes a major hurdle to deliver drugs or other potential therapeutic agents into the brain. The authors also showed that such models could be derived from a single patient, which is of special interest because it opens the possibility to monitor in the future the effects of individual mutations or polymorphisms on BBB function.

Scott Glen Canfield is currently an Assistant Professor in Cellular and Integrative Physiology at Indiana University School of Medicine in Terre Haute, Indiana. He has also co-authored a number of relevant articles in the field in the past.