الملخص
Tic disorder（TD）is a complex chronic neuropsychiatric disorder characterized by rapid，involuntary，non-hythmic，single or multi-part muscle movement or vocal twitching. Both TD and allergic diseases are related to the body's immune imbalance.The symptoms involve different parts or organs，and the pathogenesis are complex，which seriously affect the quality of life.Clinical studies have found a clear correlation between TD and allergic diseases，but the relationship mechanism is still unclear，mainly involving neuro-immune cross-disorders.This paper reviews the research progress of the relevant mechanisms of TD and allergic diseases，in order to enhance the cognition of the two diseases，and provide new ideas and directions for the etiological research and treatment of TD.
الملخص
Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.
الملخص
The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine， the modern physiological characteristics of men's diseases， and clinical practice. According to this theory， dysfunctions of the brain， heart， kidney， and semen chamber are the core mechanisms for the occurrence of premature ejaculation， and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease， while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation， we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area， neuromodulation malfunction， central neurotransmitter imbalance， endocrine disorders， and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.
الملخص
The gaseous molecules produced endogenously with several physiological functions are called gasotransmitters. Even though initially, they were predominantly thought to be of neuronal origin, recent research has clarified that they have roles far beyond that. Their primary function is maintaining the integrity of the cardiovascular system and many other parts. From the available knowledge, we have just started to learn about their roles in physiological systems that could be translated to pharmacological drug development and therapeutics. Most of the process that remains in the form of preclinical research has to go a long way toward utilizing them in therapeutics. This review addresses the various levels at which they could be potentially exploited as therapeutics and their recent entry into clinical trials.
الملخص
La etiología de la esquizofrenia no está totalmente dilucidada. Se conocen más de 100 diferentes loci de genes relacionados con esquizofrenia, la mayoría de los cuales codifican moléculas asociados a los sistemas de neurotransmisores o al neurodesarrollo. Las primeras abarcan receptores de los neurotransmisores como dopamina, GABA o glutamato y de otros neurotransmisores con menor relación, como la serotonina y la acetilcolina. También están implicadas diversas enzimas relacionadas con el metabolismo, cotransportadores y algunas proteínas intracelulares involucradas en la degradación o síntesis de dichos neurotransmisores. Entre las moléculas que intervienen en el neurodesarrollo están los factores neurotróficos (BDNF, DISC1, NRG1) y las proteínas del complemento C3 y C4, que median la respuesta inflamatoria y la poda sináptica durante el desarrollo temprano. Los productos de la producción genética involucrados en la etiología de la esquizofrenia aportan a la vulnerabilidad selectiva o al proceso de lesión que se instaura o progresa en el paciente, por tanto, su estudio es de relevancia para la comprensión de los fenómenos clínicos propios de la enfermedad.
The etiology of schizophrenia is not fully elucidated. More than 100 different gene loci related to schizophrenia are known, most of which encode molecules associated with neurotransmitter systems or neurodevelopment. These include receptors for neurotransmitters such as dopamine, GABA, or glutamate, as well as other neurotransmitters with less direct relevance, such as serotonin and acetylcholine. Various enzymes involved in metabolism, cotransporters, and intracellular proteins involved in the degradation or synthesis of said neurotransmitters are also implicated. Among the molecules involved in neurodevelopment are neurotrophic factors (BDNF, DISC1, NRG1) and complement proteins C3 and C4, which mediate the inflammatory response and synaptic pruning during early development. The genetic products involved in the etiology of schizophrenia contribute to selective vulnerability or the process of injury that is established or progresses in the patient. Therefore, their study is relevant to the understanding of the clinical phenomena associated with the disease.
A etiologia da esquizofrenia não está totalmente elucidada. Mais de 100 diferentes loci de genes relacionados à esquizofrenia são conhecidos, a maioria dos quais codifica moléculas associadas a sistemas de neurotransmissores ou neurodesenvolvimento. O primeiro inclui receptores para neurotransmissores como dopamina, GABA ou glutamato e outros neurotransmissores menos relacionados, como serotonina e acetilcolina. Também estão envolvidas várias enzimas relacionadas com o metabolismo, cotransportadores e algumas proteínas intracelulares envolvidas na degradação ou síntese dos referidos neurotransmissores. Entre as moléculas envolvidas no neurodesenvolvimento estão os fatores neurotróficos (BDNF, DISC1, NRG1) e as proteínas do complemento C3 e C4, que medeiam a resposta inflamatória e a poda sináptica durante o desenvolvimento inicial. Os produtos da produção genética envolvidos na etiologia da esquizofrenia contribuem para a vulnerabilidade seletiva ou para o processo de lesão que se instala ou progride no paciente, portanto, seu estudo é relevante para a compreensão dos fenômenos clínicos da esquizofrenia
الملخص
Background: The pathogenesis of schizophrenia has been linked to N-methyl-D-aspartate receptor (NMDAr) inhibition and DAr hyperfunction. Geraniol is a naturally occurring acyclic monoterpene with diverse pharmacological applications. We aimed to assess the effect of geraniol on schizophrenia-like symptoms, vis a vis its modulatory actions on neurochemicals in mice models of psychosis. Methods: In acute studies, male Swiss mice (n=5/group) were intraperitoneally treated with geraniol (25, 50 and 100 mg/kg), risperidone (0.5 mg/kg) or vehicle (10 ml/kg) prior to ketamine (KET) (10 mg/kg)-induced stereotypy and hyperlocomotion. In the chronic studies, mice (n=7/group) were exposed to 14 days interventions (geraniol or risperidone) following a preventive treatment with KET (20 mg/kg) from days 7-14 consecutively. The effects of treatments (e.g., geraniol or risperidone) alone and on KET-induced schizophrenia-like symptoms were investigated on the last day, 24 hours after treatments. Following that, neurochemical and neurotrophic alterations in the brain (striatum, prefrontal cortex, and hippocampus) tissues were investigated. Results: Intoxication with KET was associated with schizophrenia-like symptoms as evidenced by stereotypy behavior and hyperlocomotion. KET further induced hyperlocomotion, behavioral despair, and cognitive impairment in the chronic studies. It altered the levels of dopamine, 5-hydroxytrypamine, glutamic acid decarboxylase (GAD), acetylcholinesterase (AChE), and brain-derived neurotrophic factor (BDNF) in brain tissues. However, GER (50 and 100 mg/kg) administration significantly prevented the brain's insults caused by KET. Conclusions: Altogether, the findings support geraniol's neuroprotective activity while also adding to the body of knowledge that geraniol inhibits schizophrenia-like symptoms via modulation of neurochemical and neurotrophic pathways.
الملخص
@#The central nervous system is one of the most sensitive targets of microwave radiation. Microwave radiation can affect spatial learning and memory and neural information transmission. The effects of microwave radiation on neurotransmitters in the hippocampus and the underlying mechanisms are still unclear. This paper reviews the effects of microwave radiation on learning/memory and neurotransmitters as well as the mechanisms of action on neurotransmitters. This paper aims to provide a scientific basis for future research in this area.
الملخص
OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.
الموضوعات
Rats , Male , Animals , Moxibustion , Rats, Sprague-Dawley , Rats, Wistar , Serotonin , Hippocampus , Dopamine , Norepinephrine , Neurotransmitter Agentsالملخص
The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.
الموضوعات
Humans , Administration, Oral , Alzheimer Disease , Brain-Gut Axis , Gastrointestinal Microbiome , Neurotransmitter Agentsالملخص
Depression is one of the most common psychiatric disorders with high prevalence, disability and relapse rates, and its etiology and pathogenesis are complex and still not fully understood. Neurotransmitters play a key role in maintaining chemical homeostasis in brain, and many studies have shown a strong link between neurotransmitters and the development and treatment of depression in recent years. Therefore, studying the neurotransmitters associated with depression has the potential to provide research targets and ideas for the pathogenesis and treatment strategies of depression. This paper reviews the recent domestic and foreign research results on neurotransmitter function and the pathogenesis of depression, aiming to analyze the in-depth relationship between neurotransmitter function and the pathogenesis of depression, and provide research ideas for the follow-up ex-ploration of the pathogenesis and diagnosis and treatment strategies of depression.
الملخص
Aim To investigate the effect of marine herbal seahorse on chronic unpredictable mild stress ( CUMS ) -induced depression-like model in zebrafish. Methods Adult zebrafish were divided into control, Stress,Stress + low dose (Stress +0.044% SH) and Stress + high dose (Stress +0. 22% SH) seahorse intervention groups, and depression-like behavior was identified by novel tank test (NTT), cortisol, interleukin ( IL )-6 and interferon (IFN )-γ levels were detected by ELISA. The levels of dopamine (DA) ,norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyin-doleacetic acid (5-HIAA) were determined by high performance liquid chromatography. The mRNA expression levels of tryptophan hydroxylase(TPH)-2 and 5-HT2A receptor were measured by real-time quantitative PCR. Results Compared with the control group, the Stress group showed significantly longer latency to reach the top in NTT, significantly reduced number of transfers to the top region and top residence time, significantly increased levels of cortisol and IL-6, IFN-γ protein, significantly reduced levels of DA and 5-HT in brain as well as increased metabolism rate of 5-HT, while 5-HT2A mRNA expression was up-regulated and TPH2 mRNA expression was down-regulated. In contrast, low-dose seahorse intervention effectively reduced anxiety, decreased cortisol and IL-6 and IFN-γ concentrations, increased monoamine neurotransmitter levels and reversed dysregulation of the 5-HT ergic system in CUMS zebrafish. Conclusion Seahorse may exert an-tidepressant effects through anti-inflammation and mod¬ulation of monoamine neurotransmitter levels.
الملخص
Objective To observe the effects of plantar injection of complete Freund's adjuvant(CFA)on pain-depressive behavior and changes in hippocampal monoamine neurotransmitters in rats to establish an animal model of related comorbidity.Methods Sixteen male,8-week-old,SPF-grade healthy SD rats were randomly divided into model and control groups with eight rats in each group.In the model group,rats were anesthetized and injected with 100 μL CFA in the left hind paw to induce the comorbid chronic inflammatory pain and depression model.In the control group,rats were injected with the same volume of saline.Pain thresholds were measured using the Von Frey hair and thermal radiation instrument,and depression-like behaviors were assessed using the open field test(OFT),tail suspension test(TST),and forced swim test(FST).Enzyme-linked immunosorbent assays were used to measure 5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)in rat hippocampal tissue.Histological changes in the hippocampal area were observed by hematoxylin-eosin(HE)staining.Results Compared with the control group,the mechanical withdrawal threshold and thermal withdrawal latency in the model group were significantly decreased at 3,7,and 14 days(P<0.01).The total distance in the OFT was significantly reduced at 7 and 14 days(P<0.01),and the time spent in the center zone was significantly decreased at 14 days(P<0.01).Immobility time in the TST was significantly increased at 14 days(P<0.01),and the immobility time in the FST was significantly increased at 7 and 14 days(P<0.05,P<0.01).5-HT,DA,and NE contents in hippocampal tissue of the model group rats were significantly reduced compared with those in the control group(P<0.01),and hippocampal tissue in the model group showed pathological changes,including irregular neuronal shapes,loose and disordered arrangement,increased intercellular space,some unclear cell nuclei,and some neuronal contraction and apoptosis.Conclusions Injection of 100 μL CFA into the footpad causes pain hypersensitivity,depression-like behavior,significant reductions in monoaminergic neurotransmitters in the hippocampus,and histological changes in the hippocampus,effectively simulating the manifestations of comorbid pain and depression,and is an experimental model to study the pathological mechanisms of comorbid chronic inflammatory pain and depression.
الملخص
With complex pathogenesis, myopia is a common ophthalmology disease and a major causation for visual impairment in children. For years, studies found that neurotransmitters, such as dopamine, nitric oxide, acetylcholine, γ-aminobutyric acid, 5-hydroxytryptamine, insulin and prostaglandins, are associated with children's refractive development and axial length growth. However, there are still many disagreements in their mechanisms of action. This article makes a systematic review on the roles of neurotransmitters in the pathogenesis of myopia including neurotransmitter receptors and antagonists to clarify the influence of different neurotransmitters on the occurrence and development of myopia, thus giving a comprehensive insight into its pathogenesis, building a basis for further research on the changes of neurotransmitters and providing new ideas and directions for the prevention and treatment of myopia.
الملخص
ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.
الملخص
Depression is a common psychiatric disease that seriously affects the physical and mental health and quality of life of patients， and has become one of the major global disease burdens. The etiology of depression is intricate， and despite extensive research， its pathogenesis remains inconclusive， resulting in various hypotheses of its onset mechanisms. Presently， the primary approach for clinically treating depression involves the utilization of selective inhibitors targeting the reuptake of monoamine neurotransmitters within the central nervous system. However， these drugs are generally characterized by delayed onset of action， limited efficacy and obvious resistance. Recently， researchers have gradually turned their attention to the development of antidepressant drugs with novel mechanisms. Notably， as a category of abundantly available active ingredients in Chinese medicine， numerous pharmacological studies have demonstrated that oligosaccharides and polysaccharides possess promising antidepressant properties， such as Morindae Officinalis Radix oligosaccharides， Polygalae Radix oligosaccharide esters， Poria polysaccharides and Astragali Radix polysaccharides. Their pharmacological mechanisms are various， including enhancing the levels of monoamine neurotransmitters in the brain， inhibiting the hyperactivation of the hypothalamic-pituitary-adrenal axis（HPA axis）， increasing the expression of neurotrophic factors（NTF）， regulating immune-inflammatory responses and modulating the microbiota-gut-brain axis. Therefore， oligosaccharides and polysaccharides from Chinese medicine have become a vital source of safe and effective novel antidepressant candidates due to the potential to improve depression through integrated regulatory effects. This article aims to provide a comprehensive and systematic review of recent progress to contribute to the elucidation of the mechanisms underlying the antidepressant effects of oligosaccharides and polysaccharides derived from Chinese medicine.
الملخص
Se realiza una revisión de estudios de resonancia magnética integral y funcional, así como estudios bioquímicos en pacientes con y sin ideas suicidas. Estos estudios en pacientes con alto riesgo de suicidio presentan una disminución de volúmenes corticales en la corteza prefrontal dorso y ventrolateral. Lo importante de estos estudios es que resultan de la comparación con pacientes deprimidos con bajo riesgo de suicidio. Los estudios de resonancia magnética funcional mostraron una hipofuncionalidad del lóbulo prefrontal en los pacientes depresivos con ideas suicidas severas, que se observa como una disminución del flujo sanguíneo cerebral en las áreas lateral y ventral. Se observa una disminución del metabolismo de serotonina, en clara relación con la severidad de las ideas de muerte, también con un foco en la región lateroventral prefrontal. Dado que las funciones de la corteza prefrontal afirman al individuo en su perspectiva vital, disfunciones como las descritas debilitan la coordinación y organización del apego a la vida, quedando, por el contrario, la posibilidad de la búsqueda de la muerte. Se concluye que los pacientes depresivos con ideas suicidas tienen una alta vulnerabilidad para el intento de suicidio por la afectación de las zonas prefrontales.
A review of functional integral magnetic resonance and biochemical data from patients with and without suicidal ideation is presented. Patients with high suicidal risk show a decrease in cortical volume in ventrolateral and dorsal prefrontal cortex. These studies are compared to those of depressed patients with low suicidal risk. Functional magnetic resonance in depressed patients with severe suicidal ideation show an hypo functional prefrontal lobe, seen as a decrease in blood flow in lateral and ventral areas. There is a decrease in serotonin metabolism, clearly related to the severity of suicidal ideation, also in ventrolateral prefrontal cortex. As prefrontal cortex functions enhance vital perspectives, such dysfunctions weaken coordination and organization of attachment to life, making search for death a possibility. Authors conclude that depressed patients with suicidal ideation have a high vulnerability for suicidal intent due to changes in prefrontal areas.
الموضوعات
Humans , Suicide, Attempted , Prefrontal Cortex/physiopathology , Neurotransmitter Agents/metabolism , Depression/physiopathology , Suicidal Ideation , Magnetic Resonance Imaging , Prefrontal Cortex/metabolism , Prefrontal Cortex/diagnostic imaging , Depression/metabolismالملخص
Follow-up of patients affected by COVID-19 has unveiled remarkable findings. Among the several sequelae caused by SARS-CoV-2 viral infection, it is particularly noteworthy that patients are prone to developing depression, anxiety, cognitive disorders, and dementia as part of the post-COVID-19 syndrome. The multisystem aspects of this disease suggest that multiple mechanisms may converge towards post-infection clinical manifestations. The literature provides mechanistic hypotheses related to changes in classical neurotransmission evoked by SARS-CoV-2 infection; nonetheless, the interaction of peripherally originated classical and non-canonic peptidergic systems may play a putative role in this neuropathology. A wealth of robust findings shows that hemoglobin-derived peptides are able to control cognition, memory, anxiety, and depression through different mechanisms. Early erythrocytic death is found during COVID-19, which would cause excess production of hemoglobin-derived peptides. Following from this premise, the present review sheds light on a possible involvement of hemoglobin-derived molecules in the COVID-19 pathophysiology by fostering neuroscientific evidence that supports the contribution of this non-canonic peptidergic pathway. This rationale may broaden knowledge beyond the currently available data, motivating further studies in the field and paving ways for novel laboratory tests and clinical approaches.
الملخص
The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research
الملخص
The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research
الملخص
The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research