Paired-Pulse Inhibition and Disinhibition of the Dentate Gyrus Following Orexin Receptors Inactivation in the Basolateral Amygdala

The basolateral amygdala (BLA) has substantial effects on the neuronal transmission and synaptic plasticity processes through the dentate gyrus. Orexin neuropeptides play different roles in the sleep/wakefulness cycle, feeding, learning, and memory. The present study was conducted to investigate the function of the orexin receptors of the BLA in the hippocampal local interneuron circuits. For this, paired-pulse responses from dentate gyrus (DG) region were recorded. Within the procedure, SB-334867-A (12μg/0.5μl), and, TCS-OX2-29 (10μg/0.5μl (orexin 1 and 2 receptors antagonists, respectively), were administered into the both side of the BLA areas of the rat brain. Dimethyl sulfoxide (DMSO) was used as the solvent in the control animals with the volume of 0.5μl. Our data indicated that the paired-pulse (PP) responses were not affected by the inactivation of the orexin receptors of the BLA.

Dynamics of Choline-Containing Phospholipids in Traumatic Brain Injury and Associated Comorbidities

The incidences of traumatic brain injuries (TBIs) are increasing globally because of expanding population and increased dependencies on motorized vehicles and machines. This has resulted in increased socio-economic burden on the healthcare system, as TBIs are often associated with mental and physical morbidities with lifelong dependencies, and have severely limited therapeutic options. There is an emerging need to identify the molecular mechanisms orchestrating these injuries to life-long neurodegenerative disease and a therapeutic strategy to counter them. This review highlights the dynamics and role of choline-containing phospholipids during TBIs and how they can be used to evaluate the severity of injuries and later targeted to mitigate neuro-degradation, based on clinical and preclinical studies. Choline-based phospholipids are involved in maintaining the structural integrity of the neuronal/glial cell membranes and are simultaneously the essential component of various biochemical pathways, such as cholinergic neuronal transmission in the brain. Choline or its metabolite levels increase during acute and chronic phases of TBI because of excitotoxicity, ischemia and oxidative stress; this can serve as useful biomarker to predict the severity and prognosis of TBIs. Moreover, the effect of choline-replenishing agents as a post-TBI management strategy has been reviewed in clinical and preclinical studies. Overall, this review determines the theranostic potential of choline phospholipids and provides new insights in the management of TBI.

Transient Receptor Potential Ankyrin-1 (TRPA1) Block Protects against Loss of White Matter Function during Ischaemia in the Mouse Optic Nerve

Oligodendrocytes produce myelin, which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions, myelin is damaged, resulting in mental and physical disabilities. Recent evidence suggests that oligodendrocyte damage during ischaemia can be mediated by Transient Receptor Potential Ankyrin-1 (TRPA1), whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is constitutively active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential (CAP). Conversely, TRPA1 agonists reduce the size of the optic nerve CAP in an A-967079-sensitive manner. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of CAPs during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during, or after OGD, indicating that the TRPA1-mediated damage is occurring during both ischaemia and recovery, but importantly, that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating many white matter diseases.

Effect of short-term exposure to fluorescent red polymer microspheres on Artemia franciscana nauplii and juveniles

Microplastics (MPs) are ubiquitously present in the world’s seas with unknown potential toxic effects on aquatic ecosystems. The aim of this study was to evaluate biochemical responses caused by 1–5 μm diameter plastic fluorescent red polymer microspheres (FRM), under short-term exposure of nauplii and juveniles of Artemia franciscana, using a set of biomarkers involved in important physiological processes such as biotransformation, neuronal transmission and oxidative stress. Two FRM concentrations (0.4 and 1.6 mg mL−1) present in the water at ecologically relevant concentrations were used to study their toxicity. No significant differences were found in growth, survival and feeding behaviour of nauplii, after 2 days of exposure to both FRM concentrations. However, in juveniles, survival decreased after 5 days of exposure to FRM1.6; but no significant differences were found in either growth or feeding behaviour. It was observed that nauplii and juveniles, under short-term exposure, had the ability to ingest and egest FRM particles, although their accumulation was higher in nauplii than in juveniles, maybe related with the capacity of the latter to empty their gut content faster, in the presence of food. Regarding biomarkers responses in nauplii, all enzymatic activities increased significantly, after short-term exposure to the higher FRM concentration tested (FRM1.6), which could be related with detoxifying MPs-triggered oxidative stress. In juveniles, the inhibition of ChE and the decrease in the activity of antioxidant enzymes, after 5 days of exposure to FRM1.6, might indicate a neurotoxic effect and oxidative damage induced by FRM. This study provides further evidences that accumulation of MPs in the gut by nauplii and juveniles of A. franciscana can induce negative effects on important physiological processes with influence on their health, highlighting the general concern about the negative effects of MPs pollution on aquatic species, as well as the need to understand the mechanism of MPs toxicity and its possible impacts on environmental safety.

Copper as a Collaborative Partner of Zinc-Induced Neurotoxicity in the Pathogenesis of Vascular Dementia

Copper is an essential trace element and possesses critical roles in various brain functions. A considerable amount of copper accumulates in the synapse and is secreted in neuronal firings in a manner similar to zinc. Synaptic copper and zinc modulate neuronal transmission and contribute to information processing. It has been established that excess zinc secreted during transient global ischemia plays central roles in ischemia-induced neuronal death and the pathogenesis of vascular dementia. We found that a low concentration of copper exacerbates zinc-induced neurotoxicity, and we have demonstrated the involvement of the endoplasmic reticulum (ER) stress pathway, the stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway, and copper-induced reactive oxygen species (ROS) production. On the basis of our results and other studies, we discuss the collaborative roles of copper in zinc-induced neurotoxicity in the synapse and the contribution of copper to the pathogenesis of vascular dementia.

Beyond homeostasis: potassium and pathogenesis during bacterial infections

Potassium is an essential mineral nutrient required by all living cells for normal physiological function. Maintaining intracellular potassium homeostasis during bacterial infection is therefore a requirement for the survival of both host and pathogen. However, pathogenic bacteria require potassium transport not only to fulfill nutritional and chemiosmotic requirements, but potassium has been shown to directly modulate virulence gene expression, antimicrobial resistance, and biofilm formation. Host cells also require potassium to maintain fundamental biological processes as such as renal function, muscle contraction, and neuronal transmission, however, potassium flux also contributes to critical immunological and antimicrobial processes such as cytokine production and inflammasome activation. Here we review the role and regulation of potassium transport and signaling during infection in both mammalian and bacterial cells and highlight the importance of potassium to the success and survival of each organism.

Neuro-Immune Cross-Talk in the Striatum: From Basal Ganglia Physiology to Circuit Dysfunction

The basal ganglia network is represented by an interconnected group of subcortical nuclei traditionally thought to play a crucial role in motor learning and movement execution. During the last decades, knowledge about basal ganglia physiology significantly evolved and this network is now considered as a key regulator of important cognitive and emotional processes. Accordingly, the disruption of basal ganglia network dynamics represents a crucial pathogenic factor in many neurological and psychiatric disorders. The striatum is the input station of the circuit. Thanks to the synaptic properties of striatal medium spiny neurons (MSNs) and their ability to express synaptic plasticity, the striatum exerts a fundamental integrative and filtering role in the basal ganglia network, influencing the functional output of the whole circuit. Although it is currently established that the immune system is able to regulate neuronal transmission and plasticity in specific cortical areas, the role played by immune molecules and immune/glial cells in the modulation of intra-striatal connections and basal ganglia activity still needs to be clarified. In this manuscript, we review the available evidence of immune-based regulation of synaptic activity in the striatum, also discussing how an abnormal immune activation in this region could be involved in the pathogenesis of inflammatory and degenerative central nervous system (CNS) diseases.

Physiological and Pathological Ageing of Astrocytes in the Human Brain

Ageing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE ε4 is genetically the strongest risk factor for Alzheimer’s disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain.

Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation

TMP-CyHQ-AMPA is a photoactivatable form of a glutamate receptor agonist that has high sensitivity to 2-photon excitation. It can be used to study glutamatergic transmission with exceptional spatial-temporal resolution in complex tissue preparations.

Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders

MECP2 and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurological conditions, and perhaps modulate common presentations and pathophysiology across disorders. To clarify the mechanisms of these interactions, we develop a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the genes recognized by MeCP2 and associated to several neurological and neuropsychiatric disorders. Analysing mechanisms and pathways modulated by these genes, we find that they are involved in three main processes: neuronal transmission, immuno-reactivity, and development. Also, while the nervous system is the most relevant in the pathophysiology of the disorders, additional systems may contribute to MeCP2 action through its target genes. We tested our results with transcriptome analysis on Mecp2-null models and cells derived from a patient with RTT, confirming that the genes identified by our procedure are directly modulated by MeCP2. Thus, MeCP2 may modulate similar mechanisms in different pathologies, suggesting that treatments for one condition may be effective for related disorders.