scholarly journals Mathematical Models of Serotonin, Histamine, and Depression

2021 ◽  
Author(s):  
Janet Best ◽  
Anna Marie Buchanan ◽  
Herman Frederik Nijhout ◽  
Parastoo Hashemi ◽  
Michael C. Reed
Keyword(s):  
Mathematical Models ◽  
Serotonin Release ◽  
Experimental Techniques ◽  
Joint Research ◽  
Brain Histamine ◽  
Biological Phenomena ◽  
Serotonin Autoreceptors ◽  
Neuropsychiatric Diseases ◽  
Working Together ◽  
The Brain

The coauthors have been working together for ten years on serotonin, dopamine, and histamine and their connection to neuropsychiatric illnesses. Hashemi has pioneered many new experimental techniques for measuring serotonin and histamine in real time in the extracellular space in the brain. Best, Reed, and Nijhout have been making mathematical models of brain metabolism to help them interpret Hashemi’s data. Hashemi demonstrated that brain histamine inhibits serotonin release, giving a direct mechanism by which inflammation can cause a decrease in brain serotonin and therefore depression. Many new biological phenomena have come out of their joint research including 1) there are two different reuptake mechanisms for serotonin; 2) the effect of the serotonin autoreceptors is not instantaneous and is long-lasting even when the extracellular concentrations have returned to normal; 3) that mathematical models of serotonin metabolism and histamine metabolism can explain Hashemi’s experimental data; 4) that variation in serotonin autoreceptors may be one of the causes of serotonin-linked mood disorders. Here we review our work in recent years for biological audiences, medical audiences, and researchers who work on mathematical modeling of biological problems. We discuss the experimental techniques, the creation and investigation of mathematical models, and the consequences for neuropsychiatric diseases.

scholarly journals The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

2021 ◽  
Author(s):  
Marlaina R. Stocco ◽  
Ahmed A. El-Sherbeni ◽  
Bin Zhao ◽  
Maria Novalen ◽  
Rachel F. Tyndale
Keyword(s):  
Neurotransmitter Release ◽  
Behavioral Sensitization ◽  
Serotonin Release ◽  
Striatal Dopamine ◽  
Irreversible Inhibitor ◽  
Drug Concentrations ◽  
Metabolite Concentrations ◽  
The Brain

Abstract Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release. Results CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization. Conclusions CYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

Philosophy of Neuroscience

2016 ◽  
Author(s):  
Adina L. Roskies ◽  
Carl F. Craver
Keyword(s):  
Experimental Study ◽  
Experimental Techniques ◽  
Central Research ◽  
Philosophy Of Neuroscience ◽  
The Past ◽  
Research Areas ◽  
Potential Impact ◽  
Rich Material ◽  
The Mind ◽  
The Brain

The experimental study of the brain has exploded in the past several decades, providing rich material for both philosophers of science and philosophers of mind. In this chapter, the authors summarize some central research areas in philosophy of neuroscience. Some of these areas focus on the internal practice of neuroscience, that is, on the assumptions underlying experimental techniques, the accepted structures of explanations, the goals of integrating disciplines, and the possibility of a unified science of the mind-brain. Other areas focus outwards on the potential impact that neuroscience is having on our conception of the mind and its place in nature.

Effect of α-Fluoromethylhistidine on the Histamine Content of the Brain ofW/WvMice Devoid of Mast Cells: Turnover of Brain Histamine

1983 ◽  
Vol 41 (1) ◽  
pp. 128-134 ◽  
Author(s):  
Kazutaka Maeyama ◽  
Takehiko Watanabe ◽  
Atsushi Yamatodani ◽  
Yoshitaka Taguchi ◽  
Hiroshi Kambe ◽  
...  
Keyword(s):  
Mast Cells ◽  
Histamine Content ◽  
Brain Histamine ◽  
The Brain

DHA/EPA SUPPLEMENTATION DECREASES ANXIETY-LIKE BEHAVIOUR, BUT IT DOES NOT AMELIORATE METABOLIC PROFILE IN OBESE MALE RATS

2021 ◽  
pp. 1-25
Author(s):  
João Neto ◽  
Jeferson Jantsch ◽  
Simone de Oliveira ◽  
Matheus Filipe Braga ◽  
Luís Felipe dos Santos de Castro ◽  
...  
Keyword(s):  
Public Health Problem ◽  
Male Rats ◽  
Major Public Health Problem ◽  
Omega 3 ◽  
Elevated Plus Maze Test ◽  
Tnf Α ◽  
Plus Maze ◽  
Neuropsychiatric Diseases ◽  
The Brain ◽  
Diet Model

Abstract Obesity is a major public health problem that predisposes to several diseases and higher mortality in patients with COVID-19. Obesity also generates neuroinflammation, which predisposes to the development of neuropsychiatric diseases. Since there is a lack of effective treatments for obesity, the search for new strategies to reverse its consequences is urgent. In this perspective, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids such as DHA/EPA might reduce the harmful effects of obesity. Here, we used the cafeteria diet model to induce obesity in Wistar rats. Animals received ultra-processed food for 20 weeks, and DHA/EPA supplementation (500mg/Kg/day) was performed between the 16th and the 20th week. At the end of the experiment, it was evaluated: body weight, visceral fat deposition, plasma glucose, insulin and triglycerides, and it was also measured the levels of inflammatory cytokines TNF-α and IL-6 in plasma and liver, and TNF-α in the prefrontal cortex. The elevated plus-maze test was performed to analyze anxiety-like behaviour. Our results demonstrated that DHA/EPA could not reverse weight and fat gain and did not modify plasma dosages. However, there was a decrease in IL-6 in the liver (DHA/EPA effect: p = 0.023) and TNF-α in the brain (CAF compared to CAF+DHA/EPA, p < 0.05). Also, there was a decrease in the anxiety index in CAF+DHA/EPA compared to the CAF group (p < 0.01). Thus, DHA/EPA supplementation is helpful to reverse the consequences of obesity in the brain.

Stem cell application in neurorehabilitation

2020 ◽  
pp. 169-184
Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger A. Barker
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Adult Brain ◽  
Proper Function ◽  
Great Promise ◽  
Neuropsychiatric Diseases ◽  
Brain And Spinal Cord ◽  
The Brain

A number of diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of correct and functional neural networks. In the past, a variety of therapeutic strategies to rescue these systems have been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting endogenous or transplanting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention, along with in situ reprogramming, and opened up novel therapeutic avenues in the context of regenerative medicine. Here we review recent advances in our understanding of how endogenous stem cells may be a part of pathological processes in certain neuropsychiatric diseases and summarize recent clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS.

scholarly journals Quantitative Synaptic Biology: A Perspective on Techniques, Numbers and Expectations

2020 ◽  
Vol 21 (19) ◽  
pp. 7298
Author(s):  
Sofiia Reshetniak ◽  
Rubén Fernández-Busnadiego ◽  
Marcus Müller ◽  
Silvio O. Rizzoli ◽  
Christian Tetzlaff
Keyword(s):  
Mathematical Models ◽  
Super Resolution ◽  
Spatiotemporal Dynamics ◽  
Synaptic Function ◽  
Computational Studies ◽  
Complete Understanding ◽  
The Brain ◽  
Modelling Approaches

Synapses play a central role for the processing of information in the brain and have been analyzed in countless biochemical, electrophysiological, imaging, and computational studies. The functionality and plasticity of synapses are nevertheless still difficult to predict, and conflicting hypotheses have been proposed for many synaptic processes. In this review, we argue that the cause of these problems is a lack of understanding of the spatiotemporal dynamics of key synaptic components. Fortunately, a number of emerging imaging approaches, going beyond super-resolution, should be able to provide required protein positions in space at different points in time. Mathematical models can then integrate the resulting information to allow the prediction of the spatiotemporal dynamics. We argue that these models, to deal with the complexity of synaptic processes, need to be designed in a sufficiently abstract way. Taken together, we suggest that a well-designed combination of imaging and modelling approaches will result in a far more complete understanding of synaptic function than currently possible.

scholarly journals Dynamic N6-methyladenosine RNA methylation in brain and diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin
Keyword(s):  
Brain Development ◽  
Rna Modification ◽  
Normal Brain ◽  
Biological Processes ◽  
Future Directions ◽  
Body Of Knowledge ◽  
Neuropsychiatric Diseases ◽  
The Brain ◽  
Normal Brain Development

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.

scholarly journals Application of Raman Spectroscopy to Ancient Materials: Models and Results from Archaeometric Analyses

Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2456
Author(s):  
Daniele Chiriu ◽  
Francesca Assunta Pisu ◽  
Pier Carlo Ricci ◽  
Carlo Maria Carbonaro
Keyword(s):  
Raman Spectroscopy ◽  
Cultural Heritage ◽  
Mathematical Models ◽  
Structural Properties ◽  
Statistical Models ◽  
Experimental Techniques ◽  
Pigment Degradation ◽  
Properties Of Materials

Numerous experimental techniques of analysis find applications in many branches of the archaeometry. Among them, Raman spectroscopy carved out a niche in the field of diagnostic and conservation of cultural heritage. The exceptional ability to predict and discover the structural properties of materials set for Raman spectroscopy, an exclusive role among the analytic techniques, is further boosted when it is coupled with mathematical or statistical models able to deepen the studied phenomena. In this work, we present a review of recent studies where pairing Raman spectroscopy and mathematical models allowed achieving important results in the case of potteries, porcelains, ancient and modern paper, ancient jewelry, and pigment degradation. The potentialities of this approach are evidenced and analyzed in detail.

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