scholarly journals Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1194 ◽  
Author(s):  
Tuoxin Cao ◽  
Jessica J. Matyas ◽  
Cynthia L. Renn ◽  
Alan I. Faden ◽  
Susan G. Dorsey ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Therapeutic Potential ◽  
Recovery Of Function ◽  
Kinase Domain ◽  
Cns Injury ◽  
Trkb Receptor ◽  
Receptor Isoforms ◽  
The Central Nervous System ◽  
Injury Models

Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.

scholarly journals Antihyperalgesic Activity of Atomoxetine on Diabetes-Induced Neuropathic Pain: Contribution of Noradrenergic and Dopaminergic Systems

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2072 ◽  
Author(s):  
Mustafa Barbaros ◽  
Özgür Can ◽  
Umut Üçel ◽  
Nazlı Turan Yücel ◽  
Ümide Demir Özkay
Keyword(s):  
Neuropathic Pain ◽  
Therapeutic Potential ◽  
Sch 23390 ◽  
Withdrawal Threshold ◽  
Dopaminergic Systems ◽  
Noradrenaline Reuptake ◽  
The Central Nervous System ◽  
Streptozotocin Induced Diabetes ◽  
Noxious Stimuli ◽  
Inhibitor Drug

Atomoxetine is a selective noradrenaline reuptake inhibitor drug. Based on the knowledge that agents increasing monoamine levels in the central nervous system have therapeutic potential for neuropathic pain, it is planned to investigate the possible efficacy of atomoxetine on diabetes-induced hyperalgesia, in this study. Randall-Selitto (mechanical noxious stimuli) and Hargreaves (thermal noxious stimuli) tests were used to evaluate nociceptive perception of rats. Obtained data indicated that streptozotocin-induced diabetes causes significant decreases in the paw withdrawal threshold and paw withdrawal latency values of the animals, respectively. However, atomoxetine administered at 3 mg/kg/day for 7 and 14 days improved these diabetes-induced hyperalgesia responses. Furthermore, antihyperalgesic activity was antagonized with α-methyl-para-tyrosine methyl ester, phentolamine, propranolol, and sulpiride pre-treatments. The same effect was not reversed, however, by SCH 23390. These findings demonstrated, for the first time, that atomoxetine possesses significant antihyperalgesic activity on diabetes-induced neuropathic pain and this effect seems to be mediated by α- and β-adrenergic and D2/D3 dopaminergic receptors. Results of this present study seem to offer a new indication for an old drug; atomoxetine, but these preclinical data should first be confirmed with further well-designed clinical trials.

Steps toward recovery of function after hemilabyrinthectomy in frogs

1998 ◽  
Vol 119 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Norbert Dieringer ◽  
Hans Straka
Keyword(s):  
Time Course ◽  
Recovery Of Function ◽  
Behavioral Deficits ◽  
Afferent Fibers ◽  
Vestibular Nuclear Complex ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Necessary And Sufficient ◽  
The Brain

Removal of the labyrinthine organs on one side results in a number of severe postural and dynamic reflex deficits. Over time some of these behavioral deficits normalize again. At a chronic stage the brain of frogs exhibits a number of changes in vestibular and propriospinal circuits on the operated side that were studied in vitro. The onset of changes in the vestibular nuclear complex was delayed, became evident only after head posture had recovered by more than 50%, and was independent of the presence or absence of a degeneration of vestibular nerve afferent fibers. The time course of changes measured in the isolated spinal cord paralleled the time course of normalization of head and body posture. Results obtained after selective lesions of individual labyrinthine nerve branches show that unilateral inactivation of utricular afferent inputs is a necessary and sufficient condition to provoke postural deficits and propriospinal changes similar to those after the removal of all labyrinthine organs. The presence of multiple synaptic changes at distributed anatomic sites over different periods of time suggests that different parts of the central nervous system are involved in the normalization of different manifestations of the vestibular lesion syndrome. (Otolaryngol Head Neck Surg 1998;119:27–33.)

scholarly journals Activation and Regulation of Cellular Inflammasomes: Gaps in Our Knowledge for Central Nervous System Injury

2014 ◽  
Vol 34 (3) ◽  
pp. 369-375 ◽  
Author(s):  
Juan Pablo de Rivero Vaccari ◽  
W Dalton Dietrich ◽  
Robert W Keane
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Cns Injury ◽  
Cord Injury ◽  
Cns Trauma ◽  
The Central Nervous System ◽  
Brain And Spinal Cord

The inflammasome is an intracellular multiprotein complex involved in the activation of caspase-1 and the processing of the proinflammatory cytokines interleukin-1 β (IL-1 β) and IL-18. The inflammasome in the central nervous system (CNS) is involved in the generation of an innate immune inflammatory response through IL-1 cytokine release and in cell death through the process of pyroptosis. In this review, we consider the different types of inflammasomes (NLRP1, NLRP2, NLRP3, and AIM2) that have been described in CNS cells, namely neurons, astrocytes, and microglia. Importantly, we focus on the role of the inflammasome after brain and spinal cord injury and cover the potential activators of the inflammasome after CNS injury such as adenosine triphosphate and DNA, and the therapeutic potential of targeting the inflammasome to improve outcomes after CNS trauma.

Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review

2019 ◽  
Vol 19 (2) ◽  
pp. 75-99 ◽  
Author(s):  
Nayana Keyla Seabra de Oliveira ◽  
Marcos Rafael Silva Almeida ◽  
Franco Márcio Maciel Pontes ◽  
Mariana Pegrucci Barcelos ◽  
Carlos Henrique Tomich de Paula da Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
In Vivo Studies ◽  
Euterpe Oleracea ◽  
Case Review ◽  
The Central Nervous System

Introduction:Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins.Methods:In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí.Results:Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function.Conclusion:This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

scholarly journals Mitotherapy: Unraveling a Promising Treatment for Disorders of the Central Nervous System and Other Systemic Conditions

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1827
Author(s):  
Gabriel Nascimento-dos-Santos ◽  
Eduardo de-Souza-Ferreira ◽  
Rafael Linden ◽  
Antonio Galina ◽  
Hilda Petrs-Silva
Keyword(s):  
Therapeutic Potential ◽  
Experimental Models ◽  
Promising Therapeutic Approach ◽  
Therapy Effectiveness ◽  
The Central Nervous System ◽  
Promising Treatment ◽  
Models Of Disease ◽  
Cell To Cell Transfer

Mitochondria are key players of aerobic respiration and the production of adenosine triphosphate and constitute the energetic core of eukaryotic cells. Furthermore, cells rely upon mitochondria homeostasis, the disruption of which is reported in pathological processes such as liver hepatotoxicity, cancer, muscular dystrophy, chronic inflammation, as well as in neurological conditions including Alzheimer’s disease, schizophrenia, depression, ischemia and glaucoma. In addition to the well-known spontaneous cell-to-cell transfer of mitochondria, a therapeutic potential of the transplant of isolated, metabolically active mitochondria has been demonstrated in several in vitro and in vivo experimental models of disease. This review explores the striking outcomes achieved by mitotherapy thus far, and the most relevant underlying data regarding isolated mitochondria transplantation, including mechanisms of mitochondria intake, the balance between administration and therapy effectiveness, the relevance of mitochondrial source and purity and the mechanisms by which mitotherapy is gaining ground as a promising therapeutic approach.

scholarly journals Glial Cells and Their Contribution to the Mechanisms of Action of Cannabidiol in Neuropsychiatric Disorders

2021 ◽  
Vol 11 ◽  
Author(s):  
Franciele F. Scarante ◽  
Melissa A. Ribeiro ◽  
Ana F. Almeida-Santos ◽  
Francisco S. Guimarães ◽  
Alline C. Campos
Keyword(s):  
Glial Cells ◽  
Brain Injuries ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Molecular Targets ◽  
Neuropsychiatric Disorders ◽  
Ischemic Brain ◽  
Ppar Γ ◽  
The Central Nervous System

Cannabidiol (CBD) is a phytocannabinoid with a broad-range of therapeutic potential in several conditions, including neurological (epilepsy, neurodegenerative diseases, traumatic and ischemic brain injuries) and psychiatric disorders (schizophrenia, addiction, major depressive disorder, and anxiety). The pharmacological mechanisms responsible for these effects are still unclear, and more than 60 potential molecular targets have been described. Regarding neuropsychiatric disorders, most studies investigating these mechanisms have focused on neuronal cells. However, glial cells (astrocytes, oligodendrocytes, microglia) also play a crucial role in keeping the homeostasis of the central nervous system. Changes in glial functions have been associated with neuropathological conditions, including those for which CBD is proposed to be useful. Mostly in vitro studies have indicated that CBD modulate the activation of proinflammatory pathways, energy metabolism, calcium homeostasis, and the proliferative rate of glial cells. Likewise, some of the molecular targets proposed for CBD actions are f expressed in glial cells, including pharmacological receptors such as CB1, CB2, PPAR-γ, and 5-HT1A. In the present review, we discuss the currently available evidence suggesting that part of the CBD effects are mediated by interference with glial cell function. We also propose additional studies that need to be performed to unveil the contribution of glial cells to CBD effects in neuropsychiatric disorders.

scholarly journals Towards High-Throughput Chemobehavioural Phenomics in Neuropsychiatric Drug Discovery

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 340 ◽  
Author(s):  
Jason Henry ◽  
Donald Wlodkowic
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Innovative Methods ◽  
Approaches To Study ◽  
The Central Nervous System ◽  
Psychiatric Conditions ◽  
The Impact ◽  
Screening Approaches

Identifying novel marine-derived neuroactive chemicals with therapeutic potential is difficult due to inherent complexities of the central nervous system (CNS), our limited understanding of the molecular foundations of neuro-psychiatric conditions, as well as the limited applications of effective high-throughput screening models that recapitulate functionalities of the intact CNS. Furthermore, nearly all neuro-modulating chemicals exhibit poorly characterized pleiotropic activities often referred to as polypharmacology. The latter renders conventional target-based in vitro screening approaches very difficult to accomplish. In this context, chemobehavioural phenotyping using innovative small organism models such as planarians and zebrafish represent powerful and highly integrative approaches to study the impact of new chemicals on central and peripheral nervous systems. In contrast to in vitro bioassays aimed predominantly at identification of chemicals acting on single targets, phenotypic chemobehavioural analysis allows for complex multi-target interactions to occur in combination with studies of polypharmacological effects of chemicals in a context of functional and intact milieu of the whole organism. In this review, we will outline recent advances in high-throughput chemobehavioural phenotyping and provide a future outlook on how those innovative methods can be utilized for rapidly screening and characterizing marine-derived compounds with prospective applications in neuropharmacology and psychosomatic medicine.

scholarly journals In vivo Direct Conversion of Astrocytes to Neurons Maybe a Potential Alternative Strategy for Neurodegenerative Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Youcui Wang ◽  
Xiaoqin Zhang ◽  
Fenghua Chen ◽  
Ning Song ◽  
Junxia Xie
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Degeneration ◽  
Direct Conversion ◽  
Cns Injury ◽  
Direct Reprogramming ◽  
The Central Nervous System ◽  
Potential Alternative ◽  
Neuroregenerative Medicine

Partly because of extensions in lifespan, the incidence of neurodegenerative diseases is increasing, while there is no effective approach to slow or prevent neuronal degeneration. As we all know, neurons cannot self-regenerate and may not be replaced once being damaged or degenerated in human brain. Astrocytes are widely distributed in the central nervous system (CNS) and proliferate once CNS injury or neurodegeneration occur. Actually, direct reprogramming astrocytes into functional neurons has been attracting more and more attention in recent years. Human astrocytes can be successfully converted into neurons in vitro. Notably, in vivo direct reprogramming of astrocytes into functional neurons were achieved in the adult mouse and non-human primate brains. In this review, we briefly summarized in vivo direct reprogramming of astrocytes into functional neurons as regenerative strategies for CNS diseases, mainly focusing on neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). We highlight and outline the advantages and challenges of direct neuronal reprogramming from astrocytes in vivo for future neuroregenerative medicine.

Effect of [Asu,]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma

1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  
Keyword(s):  
Body Weight ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Regular Insulin ◽  
Prolactin Release ◽  
Saline Administration ◽  
The Central Nervous System ◽  
Plasma Prl ◽  
Male Subjects

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Sign in / Sign up

Export Citation Format

Share Document