scholarly journals Açaí: potential anticonvulsant agent

2021 ◽  
Author(s):  
Márcio Yutaka Tsukimata ◽  
Bianca Lumi Inomata da Silva ◽  
Jennison Alves Guimarães
Keyword(s):  
Cortical Neurons ◽  
Gaba Receptor ◽  
Synaptic Cleft ◽  
Clonic Seizure ◽  
Euterpe Oleracea ◽  
Inclusion Criteria ◽  
Anticonvulsant Agent ◽  
Traditional Drug ◽  
Involuntary Contraction ◽  
Drug Treatments

Background: Convulsion is an involuntary contraction of skeletal muscles. When considering vulnerable populations exposed to the mentioned pathophysiological situation, it is recognized that many of them will not have access to the indicated pharmacological treatment. Therefore, the ingestion of açai, Euterpe oleracea (EO) attenuates the problem, acting as an anticonvulsant. Objectives: evaluate the EO as an anticonvulsant agent. Design and setting: It is a bibliographic research and the data collection was done from the PubMed and Scielo databases. Methods: The descriptor used was “Euterpe oleracea” and the inclusion criteria adopted were: articles published in the last five years, available in full and publications related to epilepsy. Results: The EO acts on the GABAergic system when interacting occurs with the GABA receptor of cortical neurons and, above all, of astrocytes in an inhibitory mechanism for the uptake of the neurotransmitter GABA, that accumulates in the synaptic cleft, preventing the exaggerated neurotransmission that causes convulsions. In pentylenetetrazol-induced seizure (PTZ), EO showed some results similar to diazepam: reduced duration of tonic-clonic convulsion and increased latencies for the first myoclonic spasm and for the first generalized tonic-clonic seizure. Conclusions: Studies suggest that EO can be classified as an anticonvulsant, considering its inhibitory activity during synapses. Furthermore, the consumption of EO is more viable at a socioeconomic level compared to traditional drug treatments.

Regionally Selective Blockade of GABAergic Inhibition by Zinc in the Thalamocortical System: Functional Significance

2000 ◽  
Vol 83 (3) ◽  
pp. 1510-1521 ◽  
Author(s):  
John W. Gibbs III ◽  
Yun-Fu Zhang ◽  
Melissa D. Shumate ◽  
Douglas A. Coulter
Keyword(s):  
Cortical Neurons ◽  
Cell Voltage ◽  
Clonic Seizure ◽  
Gabaergic Inhibition ◽  
Extracellular Medium ◽  
Selective Blockade ◽  
Zinc Release ◽  
Tightly Coupled

The thalamocortical (TC) system is a tightly coupled synaptic circuit in which GABAergic inhibition originating from the nucleus reticularis thalami (NRT) serves to synchronize oscillatory TC rhythmic behavior. Zinc is colocalized within nerve terminals throughout the TC system with dense staining for zinc observed in NRT, neocortex, and thalamus. Whole cell voltage-clamp recordings of GABA-evoked responses were conducted in neurons isolated from ventrobasal thalamus, NRT, and somatosensory cortex to investigate modulation of the GABA-mediated chloride conductance by zinc. Zinc blocked GABA responses in a regionally specific, noncompetitive manner within the TC system. The regional levels of GABA blockade efficacy by zinc were: thalamus > NRT > cortex. The relationship between clonazepam and zinc sensitivity of GABAA-mediated responses was examined to investigate possible presence or absence of specific GABAAreceptor (GABAR) subunits. These properties of GABARs have been hypothesized previously to be dependent on presence or absence of the γ2 subunit and seem to display an inverse relationship. In cross-correlation plots, thalamic and NRT neurons did not show a statistically significant relationship between clonazepam and zinc sensitivity; however, a statistically significant correlation was observed in cortical neurons. Spontaneous epileptic TC oscillations can be induced in vitro by perfusion of TC slices with an extracellular medium containing no added Mg2+. Multiple varieties of oscillations are generated, including simple TC burst complexes (sTBCs), which resemble spike-wave discharge activity. A second variant was termed a complex TC burst complex (cTBC), which resembled generalized tonic clonic seizure activity. sTBCs were exacerbated by zinc, whereas cTBCs were blocked completely by zinc. This supported the concept that zinc release may modulate TC rhythms in vivo. Zinc interacts with a variety of ionic conductances, including GABAR currents, N-methyl-d-aspartate (NMDA) receptor currents, and transient potassium (A) currents.d−2-amino-5-phosphonovaleric acid and 4-aminopyridine blocked both s- and cTBCs in TC slices. Therefore NMDA and A current-blocking effects of zinc are insufficient to explain differential zinc sensitivity of these rhythms. This supports a significant role of zinc-induced GABAR modulation in differential TC rhythm effects. Zinc is localized in high levels within the TC system and appears to be released during TC activity. Furthermore application of exogenous zinc modulates TC rhythms and differentially blocks GABARs within the TC system. These data are consistent with the hypothesis that endogenously released zinc may have important neuromodulatory actions impacting generation of TC rhythms, mediated at least in part by effects on GABARs.

scholarly journals Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft Proteins

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 48 ◽  
Author(s):  
Tony Cijsouw ◽  
Austin Ramsey ◽  
TuKiet Lam ◽  
Beatrice Carbone ◽  
Thomas Blanpied ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Functional Organization ◽  
Neuronal Cell ◽  
Super Resolution ◽  
Synaptic Cleft ◽  
Surface Proteins ◽  
Mammalian Brain ◽  
Label Free ◽  
Edge Zone ◽  
Cultured Cortical Neurons

Synapses are specialized neuronal cell-cell contacts that underlie network communication in the mammalian brain. Across neuronal populations and circuits, a diverse set of synapses is utilized, and they differ in their molecular composition to enable heterogenous connectivity patterns and functions. In addition to pre- and post-synaptic specializations, the synaptic cleft is now understood to be an integral compartment of synapses that contributes to their structural and functional organization. Aiming to map the cleft proteome, this study applied a peroxidase-mediated proximity labeling approach and used the excitatory synaptic cell adhesion protein SynCAM 1 fused to horseradish peroxidase (HRP) as a reporter in cultured cortical neurons. This reporter marked excitatory synapses as measured by confocal microcopy and was targeted to the edge zone of the synaptic cleft as determined using 3D dSTORM super-resolution imaging. Proximity labeling with a membrane-impermeant biotin-phenol compound restricted labeling to the cell surface, and Label-Free Quantitation (LFQ) mass spectrometry combined with ratiometric HRP tagging of membrane vs. synaptic surface proteins was used to identify the proteomic content of excitatory clefts. Novel cleft candidates were identified, and Receptor-type tyrosine-protein phosphatase zeta was selected and successfully validated. This study supports the robust applicability of peroxidase-mediated proximity labeling for synaptic cleft proteomics and its potential for understanding synapse heterogeneity in health and changes in diseases such as psychiatric disorders and addiction.

scholarly journals Physical Activity as a Nonpharmacological Treatment for Depression: A Review

2003 ◽  
Vol 8 (2) ◽  
pp. 139-152 ◽  
Author(s):  
Wayne T. Phillips ◽  
Michaela Kiernan ◽  
Abby C. King
Keyword(s):  
Physical Activity ◽  
Low Cost ◽  
Pharmacological Intervention ◽  
Cross Sectional ◽  
Beneficial Effects ◽  
Treatment Of Depression ◽  
Traditional Drug ◽  
Drug Treatments ◽  
Research Findings

Physical activity is increasingly being cited as an alternative to more traditional drug treatments for treating depression. Although an increasing amount of research has investigated this theory, much of the literature has been criticized from a methodological perspective. Given rising concern for the increasing costs of mental health care, it is timely and important to examine valid, reliable, and objective research findings on the potential role of physical activity as a low-cost non-pharmacological intervention for the treatment of depression. This article reviews cross-sectional, longitudinal, and randomized studies that investigated the role of physical activity in the prevention and alleviation of depression. The review found that although there is undoubtedly a need for more research with a greater emphasis on methodological strength, the scientific literature is generally supportive of the beneficial effects of aerobic and nonaerobic exercise on depression in clinically and nonclinically depressed adults. Implications for public health are discussed.

scholarly journals Clarified Açaí (Euterpe oleracea) Juice as an Anticonvulsant Agent: In Vitro Mechanistic Study of GABAergic Targets

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Gabriela P. F. Arrifano ◽  
Mathieu P. Lichtenstein ◽  
José Rogério Souza-Monteiro ◽  
Marcelo Farina ◽  
Hervé Rogez ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Primary Cultures ◽  
Mechanistic Study ◽  
Gaba Uptake ◽  
Euterpe Oleracea ◽  
Adequate Treatment ◽  
Gabaergic Neurotransmission

Seizures affect about 50 million people around the world. Approximately 30% of seizures are refractory to the current pharmacological arsenal, so, the pursuit of new therapeutic alternatives is essential. Clarified Euterpe oleracea (EO) juice showed anticonvulsant properties similar to diazepam in an in vivo model with pentylenetetrazol, a GABAA receptor blocker. This study investigated the effects of EO on the main GABAergic targets for anticonvulsant drugs, analyzing the effect on the GABA receptor’s benzodiazepine and picrotoxinin binding sites and the GABA uptake. Primary cultures of cortical neurons and astrocytes were treated with EO (0–25%) for up to 90 min. [3H]Flunitrazepam and [3H]TBOB binding, [3H]GABA uptake, cell viability, and morphology were assayed. Nonlethal concentrations of EO increased agonist binding and decreased antagonist binding in cortical neurons. Low concentrations significantly inhibited GABA uptake, especially in astrocytes, suggesting an accumulation of endogenous GABA in the synaptic cleft. The results demonstrate, for the first time, that EO can improve GABAergic neurotransmission via interactions with GABAA receptor and modulation of GABA uptake. Understanding these molecular mechanisms will help in the treatment of seizures and epilepsy, especially in developing countries where geographic isolation and low purchasing power are the main barriers to access to adequate treatment.

Suppression of Hindlimb Inputs to S-I Forelimb-Stump Representation of Rats With Neonatal Forelimb Removal: GABA Receptor Blockade and Single-Cell Responses

2000 ◽  
Vol 83 (6) ◽  
pp. 3377-3387 ◽  
Author(s):  
Andrey S. Stojic ◽  
Richard D. Lane ◽  
Herbert P. Killackey ◽  
Robert W. Rhoades
Keyword(s):  
Receptive Field ◽  
Gaba Receptors ◽  
Cortical Neurons ◽  
Gaba Receptor ◽  
Single Unit ◽  
Receptive Fields ◽  
Receptor Blockade ◽  
Unit Recording ◽  
Cell Responses ◽  
Single Cell Responses

Neonatal forelimb removal in rats results in the development of inappropriate hindlimb inputs in the forelimb-stump representation of primary somatosensory cortex (S-I) that are revealed when GABAA and GABAB receptor activity are blocked. Experiments carried out to date have not made clear what information is being suppressed at the level of individual neurons. In this study, three potential ways in which GABA-mediated inhibition could suppress hindlimb expression in the S-I stump representation were evaluated: silencing S-I neurons with dual stump and hindlimb receptive fields, silencing neurons with receptive fields restricted to the hindlimb alone, and/or selective silencing of hindlimb inputs to neurons that normally express a stump receptive field only. These possibilities were tested using single-unit recording techniques to evaluate the receptive fields of S-I forelimb-stump neurons before, during, and after blockade of GABA receptors with bicuculline methiodide (for GABAA) and saclofen (for GABAB). Recordings were also made from normal rats for comparison. Of 92 neurons recorded from the S-I stump representation of neonatally amputated rats, only 2.2% had receptive fields that included the hindlimb prior to GABA receptor blockade. During GABA receptor blockade, 54.3% of these cells became responsive to the hindlimb, and in all but two cases, these same neurons also expressed a stump receptive field. Most of these cells (82.0%) expressed only stump receptive fields prior to GABA receptor blockade. In 71 neurons recorded from normal rats, only 5 became responsive to the hindlimb during GABA receptor blockade. GABA receptor blockade of cortical neurons, in both normal and neonatally amputated rats, resulted in significant enlargements of receptive fields as well as the emergence of receptive fields for neurons that were normally unresponsive. GABA receptor blockade also resulted in increases in both the spontaneous activity and response magnitudes of these neurons. These data support the conclusion that GABA mechanisms generally act to specifically suppress hindlimb inputs to S-I forelimb-stump neurons that normally express a receptive field on the forelimb stump only.

scholarly journals Translational implications of the anatomical nonequivalence of functionally equivalent cholinergic circuit motifs

2019 ◽  
Vol 116 (52) ◽  
pp. 26181-26186 ◽  
Author(s):  
Anita A. Disney ◽  
Jason S. Robert
Keyword(s):  
Species Diversity ◽  
Biomedical Research ◽  
Cortical Neurons ◽  
Basic Research ◽  
Data Driven ◽  
Anatomical Studies ◽  
Drug Treatments ◽  
Selection Of Species ◽  
Selection Of

Biomedical research is at a critical juncture, with an aging population increasingly beset by chronic illness and prominent failures to translate research from “bench to bedside.” These challenges emerge on a background of increasing “silo-ing” of experiments (and experimenters)—many investigators produce and consume research conducted in 1, perhaps 2, species—and increasing pressure to reduce or eliminate research on so-called “higher” mammals. Such decisions to restrict species diversity in biomedical research have not been data-driven and increase the risk of translational failure. To illustrate this problem, we present a case study from neuroscience: cholinergic suppression in the cortex. In all mammals studied so far, acetylcholine reduces activity in some cortical neurons. Comparative anatomical studies have shown that the mechanism behind this suppression differs between species in a manner that would render drug treatments developed in nonprimate species entirely ineffective if applied to primates (including humans). Developing clinical interventions from basic research will always require translation, either between species (e.g., using a mouse model of a human disease) or within a species (using a subset of humans as a representative sample for all humans). We argue that successful translation will require that we 1) be data-driven in our selection of species for study; 2) use (with careful attention to welfare) animals that minimize the translation gap to humans; and 3) become agile at translation, by resisting the pressures to narrow our focus to a small number of organisms, instead using species diversity as an opportunity to practice translation.

Blood Pressure Effects of Monoamine Oxidase Inhibitors — the Highs and Lows*

1987 ◽  
Vol 32 (9) ◽  
pp. 803-808 ◽  
Author(s):  
Leslie A. Cockhill ◽  
Ronald A. Remick
Keyword(s):  
Monoamine Oxidase ◽  
Postural Hypotension ◽  
Monoamine Oxidase Inhibitors ◽  
Pressure Effects ◽  
Drug Discontinuation ◽  
Hypertensive Emergencies ◽  
Rational Choices ◽  
Traditional Drug ◽  
Drug Treatments ◽  
Blood Pressure Effects

Clinical guidelines for the management of the most common side effects associated with monoamine oxidase inhibitors (postural hypotension and hypertensive episodes) are offered. When non-pharmacological interventions fail to alleviate MAOI induced postural hypotension, the use of volume expanders (salt tablets or fludrocortisone) may be effective alternatives to drug discontinuation. Phentolamine and chlorpromazine are traditional drug treatments for MAOI hypertensive emergencies. The newer drug treatments evolved in the last decade for treating hypertensive emergencies is not reflected in the psychiatric or emergency medicine literature on treating MAOI induced hypertensive states. Nifedipine, diazoxide, or sodium nitroprusside appear to be more rational choices for this problem.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Resources: Internet Resources for the Independent Medical Evaluator – 2007

2007 ◽  
Vol 12 (4) ◽  
pp. 4-7
Author(s):  
Christopher R. Brigham ◽  
Jenny Walker
Keyword(s):  
Head Trauma ◽  
Clonic Seizure ◽  
Acute Subdural Hematoma ◽  
Orbital Fracture ◽  
Orbital Wall ◽  
First Occurrence ◽  
One Year ◽  
The One ◽  
Neurological Injuries ◽  
Medial Orbital Wall

Abstract Rating patients with head trauma and multiple neurological injuries can be challenging. The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth Edition, Section 13.2, Criteria for Rating Impairment Due to Central Nervous System Disorders, outlines the process to rate impairment due to head trauma. This article summarizes the case of a 57-year-old male security guard who presents with headache, decreased sensation on the left cheek, loss of sense of smell, and problems with memory, among other symptoms. One year ago the patient was assaulted while on the job: his Glasgow Coma Score was 14; he had left periorbital ecchymosis and a 2.5 cm laceration over the left eyelid; a small right temporoparietal acute subdural hematoma; left inferior and medial orbital wall fractures; and, four hours after admission to the hospital, he experienced a generalized tonic-clonic seizure. This patient's impairment must include the following components: single seizure, orbital fracture, infraorbital neuropathy, anosmia, headache, and memory complaints. The article shows how the ratable impairments are combined using the Combining Impairment Ratings section. Because this patient has not experienced any seizures since the first occurrence, according to the AMA Guides he is not experiencing the “episodic neurological impairments” required for disability. Complex cases such as the one presented here highlight the need to use the criteria and estimates that are located in several sections of the AMA Guides.

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