Most prominent challenges in translational neuroscience and strategic solutions to bridge the gaps: Perspectives from an editorial board interrogation.

Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience.

Triarylpyrylium-based fluorescent DNA-binding dyes - facile synthesis, substituent effects, and sensing mechanism.

Novel pyrylium-based fluorescent DNA-binding dyes were developed, containing -aminoaryl groups at the positions of the pyrylium moiety. The amines are substituted with aminoalkyl groups to enhance the dye's water solubility and DNA binding affinity. With this structural modification triarylpyryliums exhibit up to 7.

Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is a devastating stroke subtype lacking effective therapies. Understanding key pathological processes related to acute brain damage will help deliver better outcomes for ICH. Herein we provide evidence that myeloid cell trafficking to the parenchyma is a conserved feature of ICH in clinical and experimental settings.

Altered molecular composition of a specific subset of prefrontal cortical excitatory synapses in schizophrenia.

Abnormal excitatory synaptic transmission in the human prefrontal cortex has been implicated in the pathophysiology of schizophrenia based primarily on genetic evidence. However, changes in synaptic function cannot be predicted from altered gene expressions, but determining the amount, density and subsynaptic distribution of synaptic proteins is the only reliable indirect readout of function. Detecting proteins in individual synapses of human postmortem tissues has been severely constrained by technical limitations.

Paradise fish (Macropodus opercularis) as a complementary translational model for emotional and cognitive function.

Zebrafish have revolutionised physiological screening in vertebrates, however, their strong sociality present challenges for interpreting behavioural assays conducted on individual subjects. To retain the advantages of the zebrafish model while addressing its limitations, we propose the use of a solitary species-the paradise fish-as a complementary model system. We compared paradise fish and zebrafish of late larval stage in social and non-social exploratory tasks, anxiety tests and in a working memory assay to assess their performance in these individual-based challenges.

The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.

Immune activation in the prenatal and early postnatal periods is increasingly implicated in the aetiology of neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, by disrupting critical neurodevelopmental processes. The impact of immune activation on brain development can be influenced by the type, timing, location, and severity of the infection. Viral, bacterial, and parasitic infections, as well as maternal autoimmune diseases, can lead to the activation of the purinergic P2X7 receptors, thereby contributing to neuroinflammation.

Optical Recordings of Unitary Synaptic Connections Reveal High and Random Local Connectivity between CA3 Pyramidal Cells.

The hippocampal CA3 region is thought to play crucial roles in episodic memory functions because of the extensive recurrent connections between CA3 pyramidal cells (CA3PCs). However, different methods provided contradicting observations about the synaptic connectivity between CA3PCs. Therefore, we estimated the connectivity rate between individual CA3PCs using a new approach that is not affected by the confounds of conventional methods.

Microgliosis, neuronal death, minor behavioral abnormalities and reduced endurance performance in alpha-ketoglutarate dehydrogenase complex deficient mice.

The alpha-ketoglutarate dehydrogenase complex (KGDHc), also known as the 2-oxoglutarate dehydrogenase complex, plays a crucial role in oxidative metabolism. It catalyzes a key step in the tricarboxylic acid (TCA) cycle, producing NADH (primarily for oxidative phosphorylation) and succinyl-CoA (for substrate-level phosphorylation, among others). Additionally, KGDHc is also capable of generating reactive oxygen species, which contribute to mitochondrial oxidative stress.

Corticothalamic feedback locally modulates network state.

As the cortex receives most of its input from the thalamus, cortical layer 6 (L6) in turn sends a massive glutamatergic projection back to the corresponding thalamic areas. L6 feedback is morphologically and physiologically distinct from driver excitatory inputs, being, according to Sherman and Guillery, a modulatory pathway, akin to classical modulators. Here we tested this hypothesis by examining the effect of L6 corticothalamic activation on thalamocortical oscillations and network state, using extracellular recordings and optogenetic stimulation.

The nonsteroidal anti-inflammatory drug meclofenamate mitigates kainic acid-induced seizures via TRPM4 inhibition.

Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated non-selective cation channel that regulates various physiological functions of excitable cells. In accordance with our previous findings, TRPM4 is known to be present and to be functionally active in hilar mossy cells where it controls seizure susceptibility. With the help of and electrophysiological and histological experiments, we investigated the effect of TRPM4 channel inhibition upon kainic acid-induced seizures.

Targeting P2X7 mitigates neurobehavioural alterations in a mouse model of post-acute sequelae of SARS-CoV-2 infection.

The COVID-19 pandemic has imposed a significant global health burden, leading to various long-term consequences, including persistent neuropsychiatric symptoms in a substantial proportion of infected individuals. This study investigates the role of the purinergic receptor P2X7 in mediating behaviour changes in a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC). We show that infection with a mouse-adapted SARS-CoV-2 strain induces anxiety- and depression-like behaviours in male mice, associated with elevated P2X7 receptor expression in the prefrontal cortex and hippocampus, as well as increased IFN-γ levels in the striatum.

Protective Effect of Selegiline (R-deprenyl) in Aminoglycoside-Induced Hearing Loss.

Aminoglycoside antibiotics remain indispensable despite their ototoxicity. Like other sensorineural forms, aminoglycoside-induced hearing loss (AGIHL) has no effective pharmacotherapy. Oxidative stress, apoptosis, excitotoxicity and inflammation are key pathological factors of the disease.

Extracellular vesicle heterogeneity through the lens of multiomics.

Extracellular vesicles (EVs) are heterogeneous in size, biogenesis, content, and function. Aggressive cancer cells release a distinct, poorly characterized, and particularly large EV subtype, namely large oncosomes (LOs). This study employs an optimized method to improve LO yields and integrates mass spectrometry and RNA sequencing (RNA-seq) to profile their molecular cargo.

Disrupted functional connectome in a rodent model of autism during social isolation.

Autism spectrum disorder (ASD) is associated with disruptions in social behavior and the neural circuitry behind it. Very little data is available on the mechanisms that are responsible for the lack of motivation to reunite with conspecifics during isolation. It is as important to investigate the neural changes that reduce motivation to end social isolation, as those underlying the reactions to social stimuli.

Distribution of NECAB1-Positive Neurons in Normal and Epileptic Brain-Expression Changes in Temporal Lobe Epilepsy and Modulation by Levetiracetam and Brivaracetam.

Calcium-binding proteins (CaBPs) are known to modulate neuronal excitability and calcium signaling, and they may play a role in the imbalances of excitation and inhibition of temporal lobe epilepsy (TLE). While parvalbumin and calretinin are well-characterized CaBPs, N-Terminal EF-Hand Calcium-Binding Protein 1 (NECAB1) remains understudied in epilepsy, despite its association with neurodegenerative conditions. In this study, we used fluorescent immunolabeling to determine the distribution of NECAB1, as well as its co-expression with parvalbumin and calretinin, in brain regions associated with the epileptic circuitry using a kainic acid-induced TLE model.

From Childhood Woes to Adult Blues: Unmasking the Role of Early Traumas, P2X7 Receptor, and Neuroinflammation in Anxiety and Depression.

Early-life stress may increase the risk of neuropsychiatric disorders via immune activation. While the purinergic signaling pathway is implicated in psychiatric disorders, the specific role of the P2X7 receptor (P2X7R) in anxiety, depression, and childhood trauma still requires further clarification. Upon chronic stress, excessive ATP release activates purinergic P2X7R signalling in the brain contributing to long-lasting neuroinflammation, which potentially promotes the development of psychiatric disorders.

The impact of the novel σ receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia.

Intracellular sigma-1 receptors (σ receptors) have a versatile function through the regulation of lipid rafts, neuroreceptors and ion channels, and can influence signal transduction and neuronal plasticity. Since decreased activity of σ receptors is a common pathological feature in the early stages of many neurological diseases, σ receptor agonists may represent a promising therapeutic tool for the treatment of these disorders. In this study, we aimed to comprehensively investigate the potential protective effects of the novel synthetic σ receptor agonist (S)-L1 against endothelial endoplasmic reticulum (ER) stress and cerebral ischemia.

Need for awareness and surveillance of long-term post-COVID neurodegenerative disorders. A position paper from the neuroCOVID-19 task force of the European Academy of Neurology.

Background: Neuropathological and clinical studies suggest that infection with SARS-CoV-2 may increase the long-term risk of neurodegeneration.

Methods: We provide a narrative overview of pathological and clinical observations justifying the implementation of a surveillance program to monitor changes in the incidence of neurodegenerative disorders in the years after COVID-19.

Results: Autopsy studies revealed diverse changes in the brain, including loss of vascular integrity, microthromboses, gliosis, demyelination, and neuronal- and glial injury and cell death, in both unvaccinated and vaccinated individuals irrespective of the severity of COVID-19.

Distinct expression of NEAT1 isoforms in Parkinson's disease models suggests different roles of the variants during the disease course.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Recently long non-coding RNAs (lncRNAs) have emerged as possible molecular hubs in the diverse pathomechanisms of the disease. Among them, NEAT1 gained particular interest due to findings suggesting both protective and deleterious effects of this lncRNA in PD models.

Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions.

Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation. Here, we investigated region-specific, dynamic changes in SERT expression following aggressive interactions and in mice subjected to early-life social adversity.

Characterization of [H]AZ12464237 as a high affinity, non-nucleotide antagonist radioligand for the P2Y receptor.

The purinergic receptor P2Y (P2YR) is a well-recognized target for anti-thrombotic agents. This receptor is also expressed in microglia, the main immune cells of the brain, where it modulates microglial activation states and inflammatory responses. To investigate P2YR-mediated actions in the central nervous system (CNS), developing novel brain-penetrant ligands and further in vitro studies on brain tissues are essential.

Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy.

Efficient treatment of temporal lobe epilepsy (TLE) remains challenging due to limited understanding of cellular and network changes and the interference of novel antiepileptic drugs (AEDs) with tissue reorganisation. This study compared the effects of brivaracetam and levetiracetam on histological alterations in key brain regions of the epileptic circuitry, namely, the hippocampus, amygdala, piriform cortex (PC), endopiriform nucleus (EPN) and paraventricular thalamic nucleus (PVT), using the kainic acid (KA) rat model of TLE. Male Wistar rats were assigned to sham-operated (SHAM), epileptic (EPI), brivaracetam- (BRV-EPI) and levetiracetam-treated (LEV-EPI) epileptic groups.

Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but may regulate neurorepair processes after experimental ischemic stroke.

Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown.

Introducing Rigidity into the GFP Chromophore via a Boron Bridge: Insights and Application in Two-Photon Imaging.

A new family of azaborine fluorophores, consisting of ten compounds, has been developed that mimics the chromophore of green fluorescent protein, with conformation locked by a hydroxyboron bridge. These fluorophores exhibit fluorescence Stokes shifts up to 100 nm (0.56 eV) and high brightness (>10 M cm) in the 408-525 nm range.

Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19.

COVID-19 is associated with diverse neurological abnormalities, but the underlying mechanisms are unclear. We hypothesized that microglia, the resident immune cells of the brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy, protein and mRNA datasets in postmortem mirror blocks of brain and peripheral organ samples from cases of COVID-19.