scholarly journals Pten is a key intrinsic factor regulating raphe 5-HT neuronal plasticity and depressive behaviors in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Chen ◽  
Wan-Kun Gong ◽  
Cui-ping Yang ◽  
Chan-Chan Shao ◽  
Ning-Ning Song ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Intrinsic Factor ◽  
Neuron Activity ◽  
Gene Transcript ◽  
Functional Changes ◽  
Electrophysiological Properties ◽  
Serotonergic Activity ◽  
Alternative Approach ◽  
The Brain ◽  
Systemic Application

AbstractSerotonin (5-HT)-based antidepressants, selective serotonin reuptake inhibitors (SSRIs) aim to enhance serotonergic activity by blocking its reuptake. We propose PTEN as a target for an alternative approach for regulating 5-HT neuron activity in the brain and depressive behaviors. We show that PTEN is elevated in central 5-HT neurons in the raphe nucleus by chronic stress in mice, and selective deletion of Pten in the 5-HT neurons induces its structural plasticity shown by increases of dendritic branching and density of PSD95-positive puncta in the dendrites. 5-HT levels are elevated and electrical stimulation of raphe neurons evokes more 5-HT release in the brain of condition knockout (cKO) mice with Pten-deficient 5-HT neurons. In addition, the 5-HT neurons remain normal electrophysiological properties but have increased excitatory synaptic inputs. Single-cell RNA sequencing revealed gene transcript alterations that may underlay morphological and functional changes in Pten-deficient 5-HT neurons. Finally, Pten cKO mice and wild-type mice treated with systemic application of PTEN inhibitor display reduced depression-like behaviors. Thus, PTEN is an intrinsic regulator of 5-HT neuron activity, representing a novel therapeutic strategy for producing antidepressant action.

scholarly journals Synaptic and epidermal accumulations of human acetylcholinesterase are encoded by alternative 3'-terminal exons.

1995 ◽  
Vol 15 (6) ◽  
pp. 2993-3002 ◽  
Author(s):  
S Seidman ◽  
M Sternfeld ◽  
R Ben Aziz-Aloya ◽  
R Timberg ◽  
D Kaufer-Nachum ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Gene Transcript ◽  
Dna Encoding ◽  
Tissue Specific ◽  
Evolutionarily Conserved ◽  
Low Salt ◽  
Catalytically Active ◽  
Specific Accumulation ◽  
The Brain ◽  
Muscle Ache

Tissue-specific heterogeneity among mammalian acetylcholinesterases (AChE) has been associated with 3' alternative splicing of the primary AChE gene transcript. We have previously demonstrated that human AChE DNA encoding the brain and muscle AChE form and bearing the 3' exon E6 (ACHE-E6) induces accumulation of catalytically active AChE in myotomes and neuromuscular junctions (NMJs) of 2- and 3-day-old Xenopus embryos. Here, we explore the possibility that the 3'-terminal exons of two alternative human AChE cDNA constructs include evolutionarily conserved tissue-recognizable elements. To this end, DNAs encoding alternative human AChE mRNAs were microinjected into cleaving embryos of Xenopus laevis. In contrast to the myotomal expression demonstrated by ACHE-E6, DNA carrying intron 14 and alternative exon E5 (ACHE-I4/E5) promoted punctuated staining of epidermal cells and secretion of AChE into the external medium. Moreover, ACHE-E6-injected embryos displayed enhanced NMJ development, whereas ACHE-I4/E5-derived enzyme was conspicuously absent from muscles and NMJs and its expression in embryos had no apparent effect on NMJ development. In addition, cell-associated AChE from embryos injected with ACHE-I4/E5 DNA was biochemically distinct from that encoded by the muscle-expressible ACHE-E6, displaying higher electrophoretic mobility and greater solubility in low-salt buffer. These findings suggest that alternative 3'-terminal exons dictate tissue-specific accumulation and a particular biological role(s) of AChE, associate the 3' exon E6 with NMJ development, and indicate the existence of a putative secretory AChE form derived from the alternative I4/E5 AChE mRNA.

Finite Difference Time Domain Simulations of Hybrid Neurotransducers Based Optical Microlasers

2020 ◽  
Author(s):  
Maurizio Manzo ◽  
Omar Cavazos
Keyword(s):  
Finite Difference ◽  
Chronic Traumatic Encephalopathy ◽  
Numerical Technique ◽  
Well Being ◽  
Infrared Light ◽  
Neuron Activity ◽  
Living Matter ◽  
Brain Functions ◽  
Laser Modes ◽  
The Brain

Abstract Different pathologies such as Alzheimer’s, Parkinson’s, Wilson’s diseases, and chronic traumatic encephalopathy due to blasts and impacts affect the brain functions altering the neuronal electrical activity. An important aspect of the brain study is the use of non-invasive, non-surgical methodologies that are suitable to the well-being of the patients. Only a portion of the electromagnetic field can be detected by applying sensors outside the scalp; in addition, surgery is often involved if sensors are applied in the subcutaneous region of the skull. Optical techniques applied to biomedical research and diagnostics have been spread during the last decades. For example, near infrared light (NIR) of spectral range goes from 800 nm to 1300 nm, it is harmless radiation for the living tissue, and can penetrate the living matter in depth as, it turns out that most of the living matter is transparent to the NIR light. Optical microlasers have been recently proposed as neurotransducers for minimally invasive neuron activity detection for the next generation of brain-computer interface (BCI) systems. They are lightweight, require low power consumption and exhibit low latency. This novel sensor that can be made of biocompatible material is coupled with a voltage sensitive dye; the fluorescence of the dye, which is excited by an external light source, is used to generate optical (laser) modes. Any variation in the neurons’ membrane electric potential via evanescent field’s perturbation turn affect the shifting of these laser modes. In order to reduce the energy required to power these devices and to improve their optical emission, metal nanoparticles can be coupled in order to use their plasmonic effect. In this paper, finite-difference timedomain (FDTD) numerical technique is used to analyze the performances on a dye-doped microlaser. Purcell effect and resonant wavelengths are observed.

Natural product-based nanomedicine: Recent advances and issues for the treatment of Alzheimer's disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Choy Ker Woon ◽  
Wong Kah Hui ◽  
Razif Abas ◽  
Muhammad Huzaimi Haron ◽  
Srijit Das ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Medicinal Plants ◽  
Drug Transport ◽  
The Elderly ◽  
Current Evidence ◽  
Alternative Approach ◽  
Progressive Neurodegeneration ◽  
The Brain

: Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and its severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano- sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material’s bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicine-based approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

scholarly journals Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessio Molfino ◽  
Gianfranco Gioia ◽  
Filippo Rossi Fanelli ◽  
Alessandro Laviano
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Proinflammatory Cytokines ◽  
Adaptive Response ◽  
Energy Homeostasis ◽  
Cancer Cachexia ◽  
Behavioral Changes ◽  
Brain Areas ◽  
Functional Changes ◽  
The Brain

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

scholarly journals Mathematical Modelling of Nitric Oxide Release Caused by Exocytosis and Determination of a Stellate Neuron Activity Function in Rat Brain

2007 ◽  
Vol 12 (3) ◽  
pp. 399-408 ◽  
Author(s):  
A. Oleinick ◽  
C. Amatore ◽  
O. Klymenko ◽  
I. Svir
Keyword(s):  
Mathematical Modelling ◽  
Neuron Activity ◽  
Nitric Oxide Release ◽  
Numerical Fitting ◽  
No Release ◽  
Initial Hypothesis ◽  
Gaussian Decomposition ◽  
The Brain ◽  
Theoretical Results

In this work we report the results of the mathematical modelling of NO◦ -release by neurons considering a series of Gaussian bursts, together with its transport in the brain by diffusion. Our analysis relies on the NO◦ -release from a neuron monitored before, during and after its patch-clamp stimulation as detected by an ultramicroelectrode introduced into a slice of living rat’s brain. The parameters of the neuron activity function have been obtained by numerical fitting of experimental data with simulated theoretical results. Within our initial hypothesis about the Gaussian decomposition of NO◦ -release that allowed drawing qualitative and quantitative conclusions about the considered neuron activity function. It is noted that since the activity function can be readily modified this signal processing may be adapted to the treatment of other and maybe more physiologically relevant hypotheses.

scholarly journals Convection-Enhanced Arborizing Catheter System Improves Local/Regional Delivery of Infusates Versus a Single-Port Catheter in Ex Vivo Porcine Brain Tissue

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Egleide Y. Elenes ◽  
Jason N. Mehta ◽  
Fang-Chi Hsu ◽  
Christopher T. Whitlow ◽  
Waldermar Debinski ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Single Port ◽  
Ex Vivo ◽  
Volume Of Distribution ◽  
Port Catheter ◽  
Convection Enhanced Delivery ◽  
Alternative Approach ◽  
The Brain ◽  
Regional Delivery ◽  
Porcine Brain Tissue

Abstract Standard treatment for glioblastoma is noncurative and only partially effective. Convection-enhanced delivery (CED) was developed as an alternative approach for effective loco-regional delivery of drugs via a small catheter inserted into the diseased brain. However, previous CED clinical trials revealed the need for improved catheters for controlled and satisfactory distribution of therapeutics. In this study, the arborizing catheter, consisting of six infusion ports, was compared to a reflux-preventing single-port catheter. Infusions of iohexol at a flow rate of 1 μL/min/microneedle were performed, using the arborizing catheter on one hemisphere and a single-port catheter on the contralateral hemisphere of excised pig brains. The volume dispersed (Vd) of the contrast agent was quantified for each catheter. Vd for the arborizing catheter was significantly higher than for the single-port catheter, 2235.8 ± 569.7 mm3 and 382.2 ± 243.0 mm3, respectively (n = 7). Minimal reflux was observed; however, high Vd values were achieved with the arborizing catheter. With simultaneous infusion using multiple ports of the arborizing catheter, high Vd was achieved at a low infusion rate. Thus, the arborizing catheter promises a highly desirable large volume of distribution of drugs delivered to the brain for the purpose of treating brain tumors.

Practical pharmacotherapy for anxiety

1997 ◽  
Vol 3 (2) ◽  
pp. 79-85 ◽  
Author(s):  
David Nutt ◽  
Caroline Bell
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Medical Profession ◽  
Behavioural Therapy ◽  
Rapid Expansion ◽  
Brain Circuits ◽  
Drug Companies ◽  
Cognitive Behavioural ◽  
Similar Growth ◽  
The Brain

Anxiety is a very common and disabling condition which has serious consequences for patients, their families and society in general. The past decade has witnessed an increase in the recognition and understanding of the problem but considerable confusion and debate remains over attitudes towards treatment. The background to this controversy dates from the late 1980s when widespread and vehement criticism of doctors and drug companies over the use of benzodiazepines began. Although the litigation was unsuccessful, it resulted in a pervading feeling of uncertainty (both within the medical profession and among patients) about prescribing or taking any drug as a treatment for anxiety. The situation has been further confounded by the split that has occurred between the proponents of pharmacological and psychological approaches to management. These controversies have left the practising clinician in an unenviable position, with few practical or relevant guidelines to follow. Developments over recent years, however, should put an end to this confusion; new pharmacotherapies such as the selective serotonin reuptake inhibitors (SSRIs) and buspirone, and older ones such as the tricyclic antidepressants (TCAs), have emerged as effective alternatives to the benzodiazepines and have been paralleled by a similar growth in effective and available psychological treatments, particularly cognitive and cognitive–behavioural therapy. This progress seems set to continue with the rapid expansion of knowledge about the brain circuits and transmitters regulating anxiety that is now emerging from imaging studies.

Economics & Practical Applications for Applied Trauma Theory

2013 ◽  
Vol 2 (2) ◽  
pp. 41-55 ◽  
Author(s):  
David S. Bathory
Keyword(s):  
World Wide ◽  
Rural Tourism ◽  
Clinical Population ◽  
Intergenerational Effects ◽  
Mass Trauma ◽  
Practical Applications ◽  
Functional Changes ◽  
The World ◽  
South Eastern Europe ◽  
The Brain

The effects of global warming are becoming apparent throughout the world. Europe has begun to experience more severe winters and increased rain (Steffen, 2011). Massive flooding in South Eastern Europe has devastated communities and repeatedly strains the economy of these regions resulting in mass trauma to the residents of multiple countries. Intergenerational effects of trauma (Kaitz, Levy, Ebstein, Faraone, & Mankuta, 2009) have been noted to be an increasing world-wide concern. These traumatic effects are not only psychologically based but result in structural and functional changes within the brain and body (van der Kolk, Roth, Pelcovitz, Sunday, & Spinazzola, 2005; Bathory, 2011; Bathory, 2012a; Bathory, 2012b). This paper explores the application of sustainable energy and rural tourism to assist mass victims of natural disaster flooding. The author provides the cultural precedents for marketing, as well as the psychoneurobiological rationale and application for an intervention to a large non-clinical population.

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