The Effects of Neurosteroids, such as Pregnenolone Sulfate and its receptor, TrpM3 in the Retina.

Pregnenolone sulfate (PregS) is the precursor to all steroid hormones and is produced in neurons in an activity dependent manner. Studies have shown that PregS production is upregulated during certain critical periods of development, such as in the first year of life in humans, during adolescence, and during pregnancy. Conversely, PregS is decreased during aging, as well as in several neurodevelopmental and neurodegenerative conditions. There are several known targets of PregS, such as a positive allosteric modulator NMDA receptors, sigma1 receptor, and as a negative allosteric modulator of GABA-A receptors. Recently a transient receptor potential channel, TrpM3 has been shown to be activated by PregS. TrpM3 is a heat sensitive (between 33-40oC), non-selective cation channel that is outwardly rectifying. PregS has been shown to increase the frequency of post-synaptic currents in the hippocampus and developing cerebellum, induce calcium transients in a subset of retinal ganglion cells, and enhance memory formation in rodents. Furthermore, PregS mediated TrpM3 activation induces calcium dependent transcription of early immediate genes, suggesting that activation of this channel may produce lasting effects on cells and systems in which it is activated. Because PregS is abundant during critical periods of development, we hypothesized that it may play a significant role during development. Furthermore, the role of PregS or its receptor TrpM3, has not previously been well characterized in the retina. To address this question, in this dissertation, we examine the role of the neurosteroid PregS and its receptor, TrpM3, on retinal waves, which are characteristic of specific stages of synaptic development and connectivity. Briefly, we show that PregS induces a TrpM3 dependent prolonged calcium transient, which is absent in the TrpM3-/- animals and increases the correlation of cell participation in waves. We also show that TrpM3 increases the frequency of post-synaptic currents, indicating a mechanism of action presynaptic to retinal ganglion cells, but that TrpM3 is expressed primarily in RGCs and Müller glia. Taken together, our results indicate that both PregS and TrpM3 are important in modulating spontaneous synaptic activity during development

What Really is `Molecule' in Molecular Communications? The Quest for Physics of Particle-based Information Carriers

Molecular communication, as implied by its name, uses molecules as information carriers for communication between objects. It has an advantage over traditional electromagnetic-wave-based communication in that molecule-based systems could be biocompatible, operable in challenging environments, and energetically undemanding. Consequently, they are envisioned to have a broad range of applications, such as in the Internet of Bio-nano Things, targeted drug delivery, and agricultural monitoring. Despite the rapid development of the field, with an increasing number of theoretical models and experimental testbeds established by researchers, a fundamental aspect of the field has often been sidelined, namely, the nature of the molecule in molecular communication. The potential information molecules could exhibit a wide range of properties, making them require drastically different treatments when being modeled and experimented upon. Therefore, in this paper, we delve into the intricacies of commonly used information molecules, examining their fundamental physical characteristics, associated communication systems, and potential applications in a more realistic manner, focusing on the influence of their own properties. Through this comprehensive survey, we aim to offer a novel yet essential perspective on molecular communication, thereby bridging the current gap between theoretical research and real-world applications

A comprehensive survey of recent advancements in molecular communication

With much advancement in the field of nanotechnology, bioengineering and synthetic biology over the past decade, microscales and nanoscales devices are becoming a reality. Yet the problem of engineering a reliable communication system between tiny devices is still an open problem. At the same time, despite the prevalence of radio communication, there are still areas where traditional electromagnetic waves find it difficult or expensive to reach. Points of interest in industry, cities, and medical applications often lie in embedded and entrenched areas, accessible only by ventricles at scales too small for conventional radio waves and microwaves, or they are located in such a way that directional high frequency systems are ineffective. Inspired by nature, one solution to these problems is molecular communication (MC), where chemical signals are used to transfer information. Although biologists have studied MC for decades, it has only been researched for roughly 10 year from a communication engineering lens. Significant number of papers have been published to date, but owing to the need for interdisciplinary work, much of the results are preliminary. In this paper, the recent advancements in the field of MC engineering are highlighted. First, the biological, chemical, and physical processes used by an MC system are discussed. This includes different components of the MC transmitter and receiver, as well as the propagation and transport mechanisms. Then, a comprehensive survey of some of the recent works on MC through a communication engineering lens is provided. The paper ends with a technology readiness analysis of MC and future research directions

Drug treatment of hypertension: focus on vascular health

Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure (BP) elevation, the vascular system is particularly important because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high BP have greater efficacy for reducing cardiovascular risk than drugs that reduce BP, but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve endothelial function and prevent vascular remodelling. Calcium channel blockers also improve endothelial function, although to a lesser extent than ACEIs and ARBs. Mineralocorticoid receptor blockers improve endothelial function and reduce arterial stiffness, and have recently become more established as antihypertensive drugs. Lifestyle factors are essential in preventing the adverse vascular changes associated with high BP and reducing associated cardiovascular risk. Clinicians and scientists should incorporate these factors into treatment decisions for patients with high BP, as well as in the development of new antihypertensive drugs that promote vascular health

Feed-forward and Feedback Control in Astrocytes for Ca2+-based Molecular Communications Nanonetworks

Synaptic plasticity depends on the gliotransmitters’ concentration in the synaptic channel. And, an abnormal concentration of gliotransmitters is linked to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and epilepsy. In this paper, a theoretical investigation of the cause of the abnormal concentration of gliotransmitters and how to achieve its control is presented through a Ca2+-signalling-based molecular communications framework. A feed-forward and feedback control technique is used to manipulate IP3 values to stabilise the concentration of Ca2+ inside the astrocytes. The theoretical analysis of the given model aims i) to stabilize the Ca2+ concentration around a particular desired level in order to prevent abnormal gliotransmitters’ concentration (extremely high or low concentration can result in neurodegeneration), ii) to improve the molecular communication performance that utilises Ca2+ signalling, and maintain gliotransmitters’ regulation remotely. It shows that the refractory periods from Ca2+ can be maintained to lower the noise propagation resulting in smaller time-slots for bit transmission, which can also improve the delay and gain performances. The proposed approach can potentially lead to novel nanomedicine solutions for the treatment of neurodegenerative diseases, where a combination of nanotechnology and gene therapy approaches can be used to elicit the regulated Ca2+ signalling in astrocytes, ultimately improving neuronal activity