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- Volume 22, Issue 4, 2023
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 22, Issue 4, 2023
Volume 22, Issue 4, 2023
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Rethinking Catatonia: New Insights from the Autism Spectrum
Authors: Liliana Dell’Osso, Daniela Toschi, Giulia Amatori and Camilla GesiInitially conceptualized as a subtype of schizophrenia, catatonia has progressively been recognized to occur in a wide variety of conditions as a kind of final common pathway for many severe mental disorders. There is a significant overlap between the fundamental symptoms of autism spectrum disorder (ASD) and catatonia, and ASD can frequently complicate catatonic states. While provocative, the hypothesis that neuroatypicality may represent the submerged structural piece underlying catatonic states is intriguing. Yet, the multifaced relationship between catatonia and ASD may provide new insights into the etiology and treatment of both disorders.
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Natural Products as Bioactive Agents in the Prevention of Dementia
Authors: Hamid Ullah, Abrar Hussain, Muhammad Asif, Faheem Nawaz and Mahmood RasoolDementia is a complex syndrome of neurological disorders which is associated with cognitive functions of the body. The present review focuses on the role and application of natural products in the treatment of dementia and related diseases. The studies highlight that there exist some potent synthetic/semisynthetic drugs that can effectively target dementia and related diseases. In contrast, despite the existence of a large library of natural products, only a few of them (galantamine, huperzine A, etc.) have been approved as drugs against dementia. This fact is not discouraging because a large number of natural products, including classes of polyphenols, alkaloids, isothiocyanates, phytocannabinoids, and terpenoids, are in the process of drug development stages against dementia and related diseases. It is because they display some promising and diverse biological activities, including antioxidant, acetylcholinesterase inhibitory activity, and anti-amyloidogenic properties, which are significantly associated with the prevention of dementia syndrome. The studies reported in the literature reveal that bioactive natural products particularly target Alzheimer’s and Parkinson’s diseases by suppressing the risks responsible for dementia. Huperzine A has been identified as a potent natural product against Alzheimer’s disease. Despite the efficient role of natural products in preventing dementia, their direct application as drugs is still limited due to some controversial results obtained from their clinical trials; however, bioassay-guided drug development studies can prove them potential drugs against dementia and related diseases. This review provides useful information for researchers, pharmacologists, and medical doctors.
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Recent Trends in Nano-Particulate Carriers for the Diagnosis and Treatment of Alzheimer’s Disease
Authors: Farhan Mazahir and Awesh K. YadavBackground: Alzheimer's disease (AD) is characterized by the presence of aggregated amyloid fibers, neurodegeneration, and loss of memory. Although "Food and Drug Administration" (FDA) approved drugs are available to treat AD, drugs that target AD have limited access to the brain and cause peripheral side effects. These peripheral side effects are the results of exposure of peripheral organs to the drugs. The blood-brain barrier (BBB) is a very sophisticated biological barrier that allows the selective permeation of various molecules or substances. This selective permeation by the BBB is beneficial and protects the brain from unwanted and harmful substances. However, this kind of selective permeation hinders the access of therapeutic molecules to the brain. Thus, a peculiar drug delivery system (nanocarriers) is required. Objective: Due to selective permeation of the “blood-brain barrier,” nanoparticulate carriers may provide special services to deliver the drug molecules across the BBB. This review article is an attempt to present the role of different nanocarriers in the diagnosis and treatment of Alzheimer's disease. Methods: Peer-reviewed and appropriate published articles were collected for the relevant information. Result: Nanoparticles not only traverse the blood-brain barrier but may also play roles in the detection of amyloid β, diagnosis, and drug delivery. Conclusion: Based on published literature, it could be concluded that nano-particulate carriers may traverse the blood-brain barrier via the transcellular pathway, receptor-mediated endocytosis, transcytosis, and may enhance the bioavailability of drugs to the brain. Hence, peripheral side effects could be avoided.
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Importance of Pharmacophore in Designing Anticonvulsant Agents
Authors: Amol Kale, Rajendra Kakde, Smita Pawar, Vishal Jagtap and Rahul DorugadeDrug design is one of the critical aspects of the drug development process. The present review focused on different heterocyclic molecules having anticonvulsant activity with structural diversity and common pharmacophoric features. For the first time (1995), Dimmock and his team introduced specific arrangements of three important pharmacophores for anticonvulsant activity. These pharmacophores include two hydrophobic binding sites and one hydrogen binding site. After a few years (2012), Pandeya modified Dimmock’s concept by adding one more pharmacophoric feature as an electron donor in the previously suggested pharmacophoric arrangement of the anticonvulsant. As a result, numerous scientists designed anticonvulsant drugs based on Dimmock’s and Pandeya’s concept. In addition, marketed anticonvulsant preparation containing Riluzole, Phenobarbital, Progabide, Ralitoline, etc., also holds the suggested pharmacophores by Dimmock and Pandeya’s pharmacophoric concept. This review mainly focuses on the compilation of reported scientific literature in the last decade on the pharmacophoric features of different heterocyclic anticonvulsants, which will help develop new anticonvulsants.
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Inter/Transgenerational Effects of Drugs of Abuse: A Scoping Review
Drug addiction is a chronic relapsing disorder that makes it a global problem. Genetics and environmental factors are the two most important factors that make someone vulnerable to drug addiction. Investigations in the past decade highlighted the role of epigenetics in the inter/transgenerational inheritance of drug addiction. A growing body of evidence showed that parental (paternal, maternal, and biparental) drug exposure before conception changes the phenotype of the offspring, which is correlated with neurochemical and neurostructural changes in the brain. The current paper reviews the effects of parental (maternal, paternal, and biparental) exposure to drugs of abuse (opioids, cocaine, nicotine, alcohol, and cannabis) before gestation in animal models.
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Dopaminergic Signaling as a Plausible Modulator of Astrocytic Toll-Like Receptor 4: A Crosstalk between Neuroinflammation and Cognition
Neuroinflammation is one of the major pathological factors leading to Alzheimer's disease (AD). The role of microglial cells in neuroinflammation associated with AD has been known for a long time. Recently, astrocytic inflammatory responses have been linked to the neuronal degeneration and pathological development of AD. Lipopolysaccharide (LPS) and Amyloid Beta (Aβ) activate astrocytes and microglial cells via toll-like 4 (TLR4) receptors leading to neuroinflammation. Reactive (activated) astrocytes mainly comprising of A1 astrocytes (A1s) are involved in neuroinflammation, while A2 astrocytes (A2s) possess neuroprotective activity. Studies link low dopamine (DA) levels during the early stages of neurodegenerative disorders with its anti-inflammatory and immuoregulatory properties. DA mediates neuroprotection via inhibition of the A1 astrocytic pathway through blockade of NF-kB and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3); and promotion of A2 astrocytic pathways leading to the formation of neurotrophic factors like BDNF and GDNF. In this current review, we have discussed the crosstalk between the dopaminergic system in astrocytic TLR4 and NF-kB in addition to NLRP3 inflammasome in the modulation of neuroinflammatory pathologies in cognitive deficits.
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Dopamine as a Potential Target for Learning and Memory: Contributing to Related Neurological Disorders
Authors: Masoumeh Kourosh-Arami, Alireza Komaki and Mohammad-Reza ZarrindastIt is well established that learning and memory are complex processes. They involve and recruit different brain modulatory neurotransmitter systems. Considerable evidence points to the involvement of dopamine (DA) in learning and memory. Manifestations of the synaptic spatial localization of the effect of DA have gained a great deal of interest. Despite the molecular cloning of the five DA receptor subtypes, the underlying signaling of the DA receptors in spatial learning and memory is less compelling. Fluctuations in the DA level in the brain are associated with many diseases that comprise deficits in learning and memory, including Parkinson's disease, Huntington’s disease, schizophrenia, and Alzheimer's disease. This review aims to briefly summarize existing information regarding the memory performance modified by DA. The signaling of the DA system, particularly examining the origin of DA-modulated memory, is also discussed. Then, several kinds of memories in which DA plays a critical role, including reward signaling, working memory, and long-term plasticity, as well as memory consolidation, are also described. Finally, memory impairment in some DA-related neurological disorders is also examined.
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The Role of the Gut Microbiota and Microbial Metabolites in the Pathogenesis of Alzheimer’s Disease
By Yi WangAlzheimer’s disease is a neurodegenerative disease that causes memory loss, cognitive dysfunction and dementia. It is a multifactorial disease involving a wide range of pathological factors that have yet to be fully understood. As proposed by scientists and supported by a growing amount of evidence in recent years, the gut microbiota plays an important role in the pathogenesis of Alzheimer’s disease via a constant bidirectional communication through the brain-gut-microbiota axis, which is a multifunctional network involving the nervous system and the peripheral circulatory system. This communication pathway facilitates the exchange of information and signals between the brain and the gut, such as microbe-derived metabolites and neurotransmitters, which allows gut microbes to influence the central nervous system. This review summarizes recent research findings on the pathological risk factors of Alzheimer’s disease, the brain-gut-microbiota axis, the role of gut microbe-derived products in neurological disorders, and clinical/preclinical studies investigating the role of the gut microbiota in Alzheimer’s disease. In addition, some suggestions for future research are proposed.
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Characteristics of Amphetamine Psychosis with Respect to the Length of Drug Exposure
Authors: Anastasia Babina, Iryna Sokolova and Mykhailo VysotskyiBackground: Over the past decade, the number of individuals requiring medical care for amphetamine-related psychosis has increased. Objective: This study aims to examine the psychological characteristics of amphetamine psychosis in drug-addicted patients depending on the length of drug exposure and compared to patients diagnosed with paranoid schizophrenia. Methods: The study was carried out in psychiatric clinic No. 1 in Kyiv (Ukraine) in 2019, involving 107 patients. Of all the participants, 50 were included in Group 1 (methamphetamine psychosis) and 57 - in Group 2 (paranoid schizophrenia). All patients were treated with medication to relieve exacerbating symptoms. They underwent extensive testing to determine the impairment severity of cognitive function, attention, and task performance during remission. Results: In Group 1, the timing of onset for paranoid symptoms depends on the length of amphetamine exposure (Spearman correlation coefficient = 0.89). The efficacy and dynamics of drug treatment in Group 2 were similar to patients in Group 1. However, the effect of reduction in Group 2 was achieved only in 4 months. Delusions, emotional disturbances, hallucinations in patients of Group 1 occurred 2.3 times more frequently than in Group 2 (p ≤ 0.05). The patients of Group 1 are characterized by the presence of disorders related to the affective and behavioral components. Conclusion. All reported exacerbations are related to amphetamine use. Patients in Group 1 learned a smaller number of words compared to those in Group 2. Besides, a large number of errors and difficulties with shifting focus were recorded.
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Danshensu Enhances Cerebral Angiogenesis in Mice by Regulating the PI3K/Akt/Mtor/VEGF Signaling Axis
Authors: Hongning Jia, Xiaoyuan Qi, Huijun Wu and Jianping WangBackground: Cerebral infraction seriously affects the life quality of patients. Danshensu has been reported to exhibit anti-inflammatory and vascular protective effects. However, the therapeutic function of Danshensu in cerebral vascular injury is still unclear. Methods: Middle cerebral artery occlusion (MCAO) was used to construct the cerebral infraction model. Wound healing and tube formation assays were used to evaluate angiogenesis in vitro. Western blot assay was used to evaluate the activation of the PI3K/Akt/mTOR signaling pathway. The laser Doppler scanner was used to measure the regional cerebral blood flow (rCBF) in the area around the infarction, and the adhesion removal test was used to measure the sensorimotor function. The Modified Neurological Severity Score was performed to evaluate the cognitive functions of mice. Results: Danshensu promoted the proliferation of bEnd.3 cells and angiogenesis in vitro. Danshensu upregulated the expression of VEGF through PI3K/Akt/mTOR signaling pathway in bEnd.3 cells. Danshensu improved rCBF restoration and attenuated the behavioral deficits in mice post-MCAO/R. Conclusion: Danshensu enhances angiogenesis through the PI3K/Akt/mTOR/VEGF signaling pathway in a mouse model of cerebral ischemic injury.
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Treatment of Major Depression with Psychotic Features and Cotard’s Syndrome after COVID-19 Infection in a Previously Healthy Patient: A Case Report
More LessBackground: COVID-19 pandemic is related to anxiety, depression, and psychotic symptoms either directly due to invasion or inflammation caused by the virus or indirectly due to related psychosocial stress: fear of infection, social isolation, and financial burden. Case Presentation: We present a 28-year-old female case of post128;COVID major depression with psychotic features and Cotard’s syndrome with no previous psychiatric history. Her complaints initially described the sadness of mood with early morning worsening, diminished interest in almost all activities, anhedonia, increased anxiety, ideas of worthlessness, hopelessness, guilt, decreased sleep, and appetite. Then, she developed severe depression with psychotic features such as delusions of persecution, poverty, and nihilism. Nihilistic delusions included a description of everything coming to an end. She thought that her organs were no more working. Later, she negated her existence and started believing that she was dead. The patient recovered after a combination of sertraline and olanzapine treatment. Conclusion: This case of a COVID-19 patient with psychotic depression and Cotard’s delusion highlights the importance of evaluating mental health status and may contribute to our understanding of the potential risk of central nervous system impairment by SARS-CoV-2 infection.
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Induced Depressive Disorder Following the First Dose of COVID-19 Vaccine
Authors: Ismail Rammouz, Jalal Doufik, Rachid Aalouane and Saïd BoujrafIntroduction: Several COVID-19 vaccines have been implemented. However, some side effects of the vaccine have been reported, which are sometimes very harmful. Reported cases and data are still very limited regarding the psychiatric side effects of the COVID-19 vaccine. To our knowledge, only one case has been reported. In this paper, we report the case of a patient who presented an acute depressive episode 24 hours after receiving his first dose of the BNT162b2mRNA vaccine. Case Report: The case was a 26-year-old man with a history of Down syndrome with moderately good autonomy for daily routine tasks. The patient, who presented hypothyroidism at 10 years old and schizophrenia at 15 years old, was doing well before the vaccination and received his first dose of the BNT162b2mRNA vaccine. Twenty-four hours later, he presented depressive symptoms that resolved spontaneously after one week. Then, fifteen days later, the symptoms reappeared, and the episode lasted for 5 weeks. The patient received 10 mg/day of escitalopram besides his usual treatment. The depressive symptoms improved considerably by the second day of treatment. Discussion: The presented case illustrated significant diagnostic challenges, especially when taking into account the sequential relationship between the COVID-19 vaccine and the occurrence of depressive symptoms. A single case of depression has been reported after the administration of the COVID-19 vaccine. Scientific evidence suggests the important role of the immune system in the pathophysiology of various psychiatric disorders, including depression. Conclusion: Health professionals must take into consideration the potential psychiatric side effects even being rare so far, especially in vulnerable subjects. Further studies are required to establish the causal effects of depressive symptoms occurring during the weeks following the COVID-19 vaccine bolus injection.
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Volumes & issues
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Volume 23 (2024)
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Volume 22 (2023)
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Volume 21 (2022)
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Volume 20 (2021)
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Volume 19 (2020)
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Volume 18 (2019)
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Volume 17 (2018)
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Volume 16 (2017)
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Volume 15 (2016)
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Volume 14 (2015)
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Volume 13 (2014)
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Volume 12 (2013)
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Volume 11 (2012)
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Volume 10 (2011)
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Volume 9 (2010)
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Volume 8 (2009)
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Volume 7 (2008)
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Volume 6 (2007)
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Volume 5 (2006)