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The astrocytes are cells which play an essential role in the functioning and interaction of neurons by feeding the respective neurons with calcium ions. Drawing inspiration from this two-way relationship in which the astrocytes influence and are influenced by the neurons by means of calcium ions, in this paper, we define and study spiking neural P systems with astrocytes producing calcium. Distinct from the usual firing rules in spiking neural P systems, the firing condition not only depends on the spikes collected in a neuron but also on the calcium units received from astrocytes. From the perspective of topological structure, the new variant is shown as a directed graph in which synapses link either astrocytes or neurons, as well as astrocytes to neurons and conversely. The computational power of spiking neural P systems with astrocytes producing calcium is investigated; it is proved that these systems using a limited number of rules are Turing universal as both number generating and number accepting devices. It is also presented how to obtain normal forms by removing forgetting rules and delays while preserving the computational power.

Curcumin, an agent traditionally utilized for its preventative action against tumorigenesis, oxidation, inflammation, apoptosis and hyperlipemia, has also been used in the treatment of Alzheimer's disease (AD). Recent advances in the study of AD have revealed astrocytes (AS) as being key factors in the early pathophysiological changes in AD. Glial fibrillary acidic protein (GFAP), a marker specific to AS, is markedly more manifest during morphological modifications and neural degeneration signature during the onset of AD. Several studies investigating the functionality of curcumin have shown that it not only inhibits amyloid sedimentation but also accelerates the disaggregation of amyloid plaque. Thus, we are interested in the relationship between curcumin and spatial memory in AD. In this study, we intend to investigate the effects of curcumin in amyloid-β (Aβ_1-40) induced AD rat models on both the behavioral and molecular levels, that is to say, on their spatial memory and on the expression of GFAP in their hippocampi. Our results were statistically significant, showing that the spatial memory of AD rats improved following curcumin treatment (p < 0.05), and that the expression of GFAP mRNA and the number of GFAP positive cells in the curcumin treated rats was decreased relative to the AD group rats (p < 0.05). Furthermore, the expression level of GFAP mRNA in hippocampal AS in the AD rats significantly increased when compared with that in the sham control (p < 0.05). Taken together, these results suggest that curcumin improves the spatial memory disorders (such disorders being symptomatic of AD) in Aβ_1-40-induced rats by down regulating GFAP expression and suppressing AS activity.

Astrocytes have important functions in the central nervous system (CNS) and are significant in our understanding of the neuronal network. Astrocytes modulate neuronal firings at both single cell level of tripartite synapses and the neuron-glial network level. Astrocytes release adenosine triphosphate (ATP) and glutamate into the neuron-glial network. These gliotransmitters diffuse over the network to form long distance signals to regulate neuron firings. In this paper, we study a neuron-glial network model that includes a diffusion of astrocytic ATP and glutamate to investigate how long distance diffusion of the gliotransmitters affects the information processing in a neuronal network. We find that gliotransmitters diffusion can compensate for the failure of information processing of interneuron network firings induced by defectively coupled synapses. Moreover, we find that calcium waves in astrocyte network and firings in interneuron network are both sensitive to the glutamate diffusion rate and feedback intensities of astrocytes on interneurons.

In this paper, a tripartite synapse network is constructed to examine external and internal triggering factors of epilepsy transition and propagation in neurons with the Epileptor-2 model. We first explore the external stimuli in the environment that induce epileptic activities and transition behaviors among Ictal Discharges (IDs) and Interictal Discharges (IIDs) states. The higher the strength and abruptness of the stimuli, the more severe is the occurrence of epilepsy within a reasonable range of parameters. Then for the internal triggering factors, the results of the tripartite synapse network, which is improved by combining the Epileptor-2 model with astrocyte by means of ion exchange and new connections, show that astrocytes can transmit normal physiological activity information and filter out abnormal discharge information of neurons. One of the causes for epileptic seizures is the abnormal release of glial neurotransmitters in astrocytes. The excessive release of glutamate causes the discharge state of neurons to transit from nonepileptic to IIDs, IDs and tonic, while adenosine triphosphate can alleviate epilepsy. Meanwhile, the synapse dysfunction of an astrocyte-free network can also lead to seizures, and the epilepsy propagation ability of a tripartite synapse network becomes weaker than that of an astrocyte-free network. Our research is expected to provide some theoretical basis for the therapeutic approach to curing epilepsy in the intracellular and extracellular contexts.

ASIA-PACIFIC — Entries open for the USD170,000 Ryman Prize.

ASIA-PACIFIC — Singapore scientists discover new ways to help us understand how the body fights cancer.

ASIA-PACIFIC — New discovery reveals acne, acne scarring and osteoporosis may be related to collagen issues.

ASIA-PACIFIC — Making the switch: Potent anticancer liposomal drugs.

ASIA-PACIFIC — Blood vessel-forming cells involved in aggressive brain tumour.

ASIA-PACIFIC — New medical device for safe growth of neural stem cells using nanotechnology.

ASIA-PACIFIC — HKU to collaborate on biomedical innovation with Institut Pasteur and Hong Kong Science and Technology Parks Corporation.

REST OF THE WORLD — Could the eye be the window to brain degeneration?

REST OF THE WORLD — High vitamin D levels linked to lower cholesterol in children.

Glaucoma is considered a group of neurodegenerative diseases that damage the optic disc and result in a reduction of the field of vision. High intraocular pressure-induced deformation of optic nerve head (ONH) may compress the optic nerve and affect axonal transport. This study aims to show experimental observations: the activated astrocytes under high intraocular pressure play an important role in compression of optic nerve and block of axonal transport. Four-week duration of ocular hypertension (more than 20mm Hg) rats induced by cauterizing of three episcleral vessels and administering a fluorouracil subconjunctival injection in the right eye were enrolled and the left eyes of all the rats were used as a self-control. The axonal transport of the optic nerve was examined by a confocal laser scanning microscope after intravitreally injecting rhodamine-$\beta$-isothiocyanate. The morphology of the optic nerve head was examined by hematoxylin–eosin (HE) staining, immunofluorescence staining and transmission electron microscopy (TEM). The results showed transport of rhodamine-$\beta$-isothiocyanate was blocked in the experimental group, and fluorescent dye accumulated around the ONH. The nucleus counts of the coronal section kidney-shaped area showed that the number of cell nucleus in experimental eye was more than that of the control according to the results of HE staining. The increased collagen fibers in ONH were observed. The density of the glial fibrillary acidic protein in experimental eyes was a little bit higher than that in the control group by quantify analysis of the expression. The obvious changes of microstructure of the ONH also were found according to the images of TEM. It can be concluded that the activated astrocytes might squeeze the optic nerve, likely leading to optic nerve distortion and axonal flow blockage.

As discussed in other articles in this issue, chemical emergence may have led to the appearance of life on the pre-biotic earth, but it is even more obviously clear that emergence continues in living systems, producing complex phenomena such as ordering, biorhythms and even, possibly, consciousness. The role of continuing emergence in living systems is reviewed here with special attention to the Peroxidase–Oxidase reaction and neurochemical systems. For the latter, we review the role of subnetwork dynamics in epilepsy and an intriguing new possiblity that calcium waves in fields of astrocytes in the brain may be involved in the spread of epileptic seizures.

Most biological tissues are soft viscoelastic materials with elastic moduli ranging from approximately 100 to 100,000 Pa. Recent studies have examined the effect of substrate rigidity on cell structure and function, and many, but not all cell types exhibit a strong response to substrate stiffness. Some blood cells such as platelets and neutrophils have indistinguishable structures on hard and soft materials as long as they are sufficiently adhesive, whereas many cell types, including fibroblasts and endothelial cells spread much more strongly on rigid compared to soft substrates. A few cell types such as neurons appear to extend better on very soft materials. The different response of astrocytes and neurons to the stiffness of their substrate results in preferential growth of neurons on soft gels and astrocytes on hard gels, and suggests that preventing rigidification of damaged central nervous system tissue after injury may have utility in wound healing. How cells sense substrate stiffness is unknown. One candidate protein, filamin A, which responds to externally derived stresses, was tested in melanoma cells. Cells devoid of filamin A retain the ability to sense substrate stiffness, suggesting that other proteins are required for stiffness sensing.

Dexamethasone is a synthetic corticosteroid that has historically been used to treat inflammation, such as from osteoarthritis, spinal cord injury and, more recently, COVID-19. The mechanism of action of dexamethasone is generally known to include attenuation of pro-inflammatory responses as well as upregulation of anti-inflammatory elements. A major issue with the use of dexamethasone is its delivery, as it is normally administered in large quantities via methods like bolus injection to attempt to maintain sufficient concentrations days or weeks after administration. In this review, we examine the mechanism of action of dexamethasone and its effects on three major cell types in the context of specific diseases: macrophages in the context of COVID, chondrocytes in the context of osteoarthritis, and astrocytes in the context of neuro-inflammatory disease. From this, we identify the key proinflammatory cytokines interleukin-1 (IL-1) and Tumor Necrosis Factor alpha (TNF-a) as universal effectors of inflammation that should be targeted alongside dexamethasone administration. Additionally, we review current extended release dosing mechanisms for dexamethasone to act over periods of weeks and months. We suggest that dual treatment of dexamethasone with IL-1 and/or TNF-a monoclonal antibodies will be an effective immediate treatment for inflammation, while the addition of fully developed dexamethasone extended release mechanisms will allow for effective long-term control of inflammatory disease.

The physiological role of metallothionein (MT) has been a topic of growing interest, particularly with regard to a potential therapeutic application in trauma of the central nervous system (CNS). An increasing number of studies describe the protective, regenerative, and anti-inflammatory properties of MT-I and MT-II isoforms (MT-I/MT-II) in the context of in vitro and animal models, using, for example, MT-I/MT-II null, overexpressing, or injected mice following induced CNS trauma or disease. MT-I/MT-II respond to trauma by upregulation, and may have roles in metal ion homeostasis and free radical scavenging. Notably, a direct action of MT-I/MT-II on neurons has been shown using in vitro models, whereby the application of exogenous MT-I/MT-II directly increases neurite outgrowth of young neurons and regeneration of injured, mature neurons. The expression and putative functions of MT within the injured CNS will be addressed within this chapter, with particular regard to the MT-I/MT-II isoforms that display neuroprotective and regenerative properties. Intriguingly, a further member of the MT family, MT-III, shows high homology to MT-I/MT-II, yet has a contrasting effect on neuron growth and survival in some models.