Current Neuropharmacology最新文献

{"title":"Magnetic Resonance Imaging and Nuclear Imaging of Parkinsonian Disorders: Where do we go from here?","authors":"Félix-Antoine Savoie, David J Arpin, David E Vaillancourt","doi":"10.2174/1570159X21666230801140648","DOIUrl":"10.2174/1570159X21666230801140648","url":null,"abstract":"<p><p>Parkinsonian disorders are a heterogeneous group of incurable neurodegenerative diseases that significantly reduce quality of life and constitute a substantial economic burden. Nuclear imaging (NI) and magnetic resonance imaging (MRI) have played and continue to play a key role in research aimed at understanding and monitoring these disorders. MRI is cheaper, more accessible, nonirradiating, and better at measuring biological structures and hemodynamics than NI. NI, on the other hand, can track molecular processes, which may be crucial for the development of efficient diseasemodifying therapies. Given the strengths and weaknesses of NI and MRI, how can they best be applied to Parkinsonism research going forward? This review aims to examine the effectiveness of NI and MRI in three areas of Parkinsonism research (differential diagnosis, prodromal disease identification, and disease monitoring) to highlight where they can be most impactful. Based on the available literature, MRI can assist with differential diagnosis, prodromal disease identification, and disease monitoring as well as NI. However, more work is needed, to confirm the value of MRI for monitoring prodromal disease and predicting phenoconversion. Although NI can complement or be a substitute for MRI in all the areas covered in this review, we believe that its most meaningful impact will emerge once reliable Parkinsonian proteinopathy tracers become available. Future work in tracer development and high-field imaging will continue to influence the landscape for NI and MRI.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1583-1605"},"PeriodicalIF":5.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.","authors":"Zhiyong Gao, Meihong Xiu, Jiahong Liu, Fengchun Wu, Xiangyang Zhang","doi":"10.2174/1570159X22666231019105328","DOIUrl":"10.2174/1570159X22666231019105328","url":null,"abstract":"<p><strong>Background: </strong>It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients.</p><p><strong>Methods: </strong>The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12.</p><p><strong>Results: </strong>Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC.</p><p><strong>Conclusion: </strong>Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1733-1741"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction.","authors":"Kewarin Jinawong, Chanon Piamsiri, Nattayaporn Apaijai, Chayodom Maneechote, Busarin Arunsak, Wichwara Nawara, Chanisa Thonusin, Hiranya Pintana, Nipon Chattipakorn, Siriporn C Chattipakorn","doi":"10.2174/1570159X22666240131114913","DOIUrl":"10.2174/1570159X22666240131114913","url":null,"abstract":"<p><strong>Background: </strong>We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI).</p><p><strong>Objective: </strong>To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril.</p><p><strong>Methods: </strong>Male rats were assigned to either sham or MI operation. In the MI group, rats with an ejection Fraction less than 50% were included, and then they received one of the following treatments for 5 weeks: vehicle, enalapril, Mdivi-1, or M1. Cognitive function was tested, and the brains were used for molecular study.</p><p><strong>Results: </strong>MI rats exhibited cardiac dysfunction with systemic oxidative stress. Cognitive impairment was found in MI rats, along with dendritic spine loss, blood-brain barrier (BBB) breakdown, brain mitochondrial dysfunction, and decreased mitochondrial and increased glycolysis metabolism, without the alteration of APP, BACE-1, Tau and p-Tau proteins. Treatment with Mdivi-1, M1, and enalapril equally improved cognitive function in MI rats. All treatments decreased dendritic spine loss, brain mitochondrial oxidative stress, and restored mitochondrial metabolism. Brain mitochondrial fusion was recovered only in the Mdivi-1-treated group.</p><p><strong>Conclusion: </strong>Mitochondrial dynamics modulators improved cognitive function in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction and the enhancement of mitochondrial metabolism. In addition, this mitochondrial fission inhibitor increased mitochondrial fusion in MI rats.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1749-1760"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic Stroke and Autophagy: The Roles of Long Non-Coding RNAs.","authors":"Longqiang Ouyang, Wenyan Xia, Ameen Abdulhasan Al-Alwany, Reena Gupta, Ibrokhim Sapaev, Sami G Almalki, Saud Almawash, Rand Ali Ziyad, Ahmed Hussien Alawadi, Ali Alsalamy","doi":"10.2174/1570159X22666240704123701","DOIUrl":"10.2174/1570159X22666240704123701","url":null,"abstract":"<p><p>Ischemic stroke is a significant cause of morbidity and mortality worldwide. Autophagy, a process of intracellular degradation, has been shown to play a crucial role in the pathogenesis of ischemic stroke. Long non-coding RNAs (lncRNAs) have emerged as essential regulators of autophagy in various diseases, including ischemic stroke. Recent studies have identified several lncRNAs that modulate autophagy in ischemic stroke, including MALAT1, MIAT, SNHG12, H19, AC136007. 2, C2dat2, MEG3, KCNQ1OT1, SNHG3, and RMRP. These lncRNAs regulate autophagy by interacting with key proteins involved in the autophagic process, such as Beclin-1, ATG7, and LC3. Understanding the role of lncRNAs in regulating autophagy in ischemic stroke may provide new insights into the pathogenesis of this disease and identify potential therapeutic targets for its treatment.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"85-97"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise as Treatment for \"Stress-Related\" Mental Disorders.","authors":"Antonia Bendau, Moritz Bruno Petzold, Jan Kaminski, Jens Plag, Andreas Ströhle","doi":"10.2174/1570159X22666230927103308","DOIUrl":"10.2174/1570159X22666230927103308","url":null,"abstract":"<p><p>The beneficial impact of physical activity on preventing and treating mental disorders has captured growing (research) interest. This article aims to provide a concise overview of essential evidence regarding the effectiveness and underlying mechanisms of physical activity for individuals with mental disorders clustered as \"stress-related\" conditions. Empirical findings (e.g., longitudinalprospective studies, interventional randomized-controlled-trials, reviews, meta-analyses) regarding the effects of physical activity in the prevention and treatment of stress-related mental disorders are summarized. Furthermore, potential mechanisms underlying these effects are discussed, and recommendations regarding the use of physical activity are outlined. The majority of studies indicate good efficacy of physical activity in prospectively lowering the risk for the incidence of subsequent stress-related mental disorders as well as in the treatment of manifest disorders. Most evidence targets unipolar depressive disorder and, secondly, anxiety disorders. Research regarding posttraumatic stress disorder, obsessive-compulsive disorders, and somatoform disorders is promising but scarce. Physical activity seems to be useful as a stand-alone-treatment as well as in combination with other psychotherapeutic or pharmacological treatments. Multiple intertwined physiological, psychological, and social mechanisms are assumed to mediate the beneficial effects. Recommendations regarding physical activity can orientate on official guidelines but should consider the individual needs and circumstances of each subject. In summary, physical activity seems to be effective in the prevention and treatment of stressrelated mental disorders and, therefore, should be fostered in healthcare-settings. Future studies are needed to clarify partly inconsistent patterns of results and to close research gaps, e.g., concerning somatoform disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"420-436"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Development of Stress Reactivity and Regulation in Children and Adolescents.","authors":"Clarissa Filetti, Finola Kane-Grade, Megan Gunnar","doi":"10.2174/1570159X21666230808120504","DOIUrl":"10.2174/1570159X21666230808120504","url":null,"abstract":"<p><p>Adversity experienced in early life can have detrimental effects on physical and mental health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA) axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspectives that guide stress reactivity and regulation research, the anatomy and physiology of the axis, developmental changes in the axis and its regulation, brain systems regulating stress, the role of genetic and epigenetics variation in axis development, sensitive periods in stress system calibration, the social regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiology and development. Understanding the development of stress reactivity and regulation is crucial for uncovering how early adverse experiences influence mental and physical health.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"395-419"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Basal Ganglia and Mesencephalic Locomotor Region Connectivity Matrix.","authors":"Nicolás A Morgenstern, Maria S Esposito","doi":"10.2174/1570159X21666230809112840","DOIUrl":"10.2174/1570159X21666230809112840","url":null,"abstract":"<p><p>Although classically considered a relay station for basal ganglia (BG) output, the anatomy, connectivity, and function of the mesencephalic locomotor region (MLR) were redefined during the last two decades. In striking opposition to what was initially thought, MLR and BG are actually reciprocally and intimately interconnected. New viral-based, optogenetic, and mapping technologies revealed that cholinergic, glutamatergic, and GABAergic neurons coexist in this structure, which, in addition to extending descending projections, send long-range ascending fibers to the BG. These MLR projections to the BG convey motor and non-motor information to specific synaptic targets throughout different nuclei. Moreover, MLR efferent fibers originate from precise neuronal subpopulations located in particular MLR subregions, defining independent anatomo-functional subcircuits involved in particular aspects of animal behavior such as fast locomotion, explorative locomotion, posture, forelimb- related movements, speed, reinforcement, among others. In this review, we revised the literature produced during the last decade linking MLR and BG. We conclude that the classic framework considering the MLR as a homogeneous output structure passively receiving input from the BG needs to be revisited. We propose instead that the multiple subcircuits embedded in this region should be taken as independent entities that convey relevant and specific ascending information to the BG and, thus, actively participate in the execution and tuning of behavior.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1454-1472"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9967183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Roles of Microglia in Blood-Brain Barrier Integrity in Aging and Neurodegeneration.","authors":"Simeng Zhang, Rui Meng, Muzhou Jiang, Hong Qing, Junjun Ni","doi":"10.2174/1570159X21666230203103910","DOIUrl":"10.2174/1570159X21666230203103910","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a highly selective interface between the blood and the brain parenchyma. It plays an essential role in maintaining a specialized environment for central nervous system function and homeostasis. The BBB disrupts with age, which contributes to the development of many age-related disorders due to central and peripheral toxic factors or BBB dysfunction. Microglia, the resident innate immune cells of the brain, have recently been explored for their ability to directly and indirectly regulate the integrity of the BBB. This review will focus on the current understanding of the molecular mechanisms utilized by microglia to regulate BBB integrity and how this becomes disrupted in aging and age-associated diseases. We will also discuss the rationale for considering microglia as a therapeutic target to prevent or slow down neurodegeneration.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1189-1204"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10653233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathways from the Superior Colliculus to the Basal Ganglia.","authors":"Fernando Falkenburger Melleu, Newton Sabino Canteras","doi":"10.2174/1570159X21666230911102118","DOIUrl":"10.2174/1570159X21666230911102118","url":null,"abstract":"<p><p>The present work aims to review the structural organization of the mammalian superior colliculus (SC), the putative pathways connecting the SC and the basal ganglia, and their role in organizing complex behavioral output. First, we review how the complex intrinsic connections between the SC's laminae projections allow for the construction of spatially aligned, visual-multisensory maps of the surrounding environment. Moreover, we present a summary of the sensory-motor inputs of the SC, including a description of the integration of multi-sensory inputs relevant to behavioral control. We further examine the major descending outputs toward the brainstem and spinal cord. As the central piece of this review, we provide a thorough analysis covering the putative interactions between the SC and the basal ganglia. To this end, we explore the diverse thalamic routes by which information from the SC may reach the striatum, including the pathways through the lateral posterior, parafascicular, and rostral intralaminar thalamic nuclei. We also examine the interactions between the SC and subthalamic nucleus, representing an additional pathway for the tectal modulation of the basal ganglia. Moreover, we discuss how information from the SC might also be relayed to the basal ganglia through midbrain tectonigral and tectotegmental projections directed at the substantia nigra compacta and ventrotegmental area, respectively, influencing the dopaminergic outflow to the dorsal and ventral striatum. We highlight the vast interplay between the SC and the basal ganglia and raise several missing points that warrant being addressed in future studies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1431-1453"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of Brain-derived Neurotrophic Factor, Exercise, and Fear Extinction: Implications for Post-traumatic Stress Disorder.","authors":"Emily J Antolasic, Emily J Jaehne, Maarten van den Buuse","doi":"10.2174/1570159X21666230724101321","DOIUrl":"10.2174/1570159X21666230724101321","url":null,"abstract":"<p><p>Brain-Derived Neurotrophic Factor (BDNF) plays an important role in brain development, neural plasticity, and learning and memory. The Val66Met single-nucleotide polymorphism is a common genetic variant that results in deficient activity-dependent release of BDNF. This polymorphism and its impact on fear conditioning and extinction, as well as on symptoms of post-traumatic stress disorder (PTSD), have been of increasing research interest over the last two decades. More recently, it has been demonstrated that regular physical activity may ameliorate impairments in fear extinction and alleviate symptoms in individuals with PTSD via an action on BDNF levels and that there are differential responses to exercise between the Val66Met genotypes. This narrative literature review first describes the theoretical underpinnings of the development and persistence of intrusive and hypervigilance symptoms commonly seen in PTSD and their treatment. It then discusses recent literature on the involvement of BDNF and the Val66Met polymorphism in fear conditioning and extinction and its involvement in PTSD diagnosis and severity. Finally, it investigates research on the impact of physical activity on BDNF secretion, the differences between the Val66Met genotypes, and the effect on fear extinction learning and memory and symptoms of PTSD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"543-556"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}