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Atypical antipsychotics, more than just an antipsychotic

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Neural Regeneration Research 2020年第8期15卷 1477-1478页

作者： Hiram Tendilla-Beltrán Gonzalo Flores Laboratorio de fisiología de la Conducta Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCDMXMexico Laboratorio de Neuropsiquiatría Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaPueblaMexico

Antipsychotics are the prescribed drugs for schizophrenia.The first substance used for antipsychotic purposes appeared in 1952 and it was a general anesthetic:chlorpromazine.The use of this drug was mainly because of its effects on violent behavior instead of sedation in patients,which“controls”the psychotic episodes and prevents psychosis relapse.Since then,pharmaceutical antipsychotics have been developed,producing second-generation or atypical drugs.These drugs arose with the synthesis of clozapine in the late‘50s,which represented(and still represent)the“guide molecule”for the development of these substances,because of its effectiveness on the symptomatology of the disease.

关键词： prescribed synthesis drugs

Potential role of noise to improve intracortical microstimulation in tactile neuroprostheses

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Neural Regeneration Research 2021年第8期16卷 1533-1534页

作者： Pedro Mabil Nayeli Huidobro Amira Flores Elias Manjarrez Laboratory of Integrative Neurophysiology Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaCPMéxico

The intracortical microstimulation(ICMS) from 40 to 100 μA is useful to elicit tactile sensations,which could be employed in neuroprostheses to control the robotic arms' movement.However,this electrical current applied for prolonged periods of time could damage the neuronal tissue.Therefore,there is a necessity to create new strategies for the practical use of ICMS in a safe intensity range for potential clinical applications in tetraplegic patients.Here we describe crucial studies supporting the use of electrical and optical noise to guarantee a safe ICMS delivered through brain-machine interface technologies.

关键词： guarantee supporting sensation

Preliminary examination of early neuroconnectivity features in the R6/1 mouse model of Huntington's disease by ultra-high field diffusion MRI

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Neural Regeneration Research 2022年第5期17卷 983-986页

作者： Rodolfo G.Gatto Carina Weissmann department of Bioengineering the University of Illinois at ChicagoChicagoILUSA Instituto de Fisiología Biología Molecular y Neurociencias-IFIBYNECONICET Universidad de Buenos AiresBuenos AiresArgentina

During the last decades,advances in the understanding of genetic,cellular,and microstructural alterations associated to Huntington's disease(HD)have improved the understanding of this progressive and fatal illness.However,events related to early neuropathological events,neuroinflammation,deterioration of neuronal connectivity and compensatory mechanisms still remain vastly unknown.Ultra-high field diffusion MRI(UHFD-MRI)techniques can contribute to a more comprehensive analysis of the early microstructural changes observed in HD.In addition,it is possible to evaluate if early imaging microstructural parameters might be linked to histological biomarkers.Moreover,qualitative studies analyzing histological complexity in brain areas susceptible to neurodegeneration could provide information on inflammatory events,compensatory increase of neuroconnectivity and mechanisms of brain repair and regeneration.The application of ultra-high field diffusion-MRI technology in animal models,particularly the R6/1 mice(a common preclinical mammalian model of HD),provide the opportunity to analyze alterations in a physiologically intact model of the disease.Although some disparities in volumetric changes across different brain structures between preclinical and clinical models has been documented,further application of different diffusion MRI techniques used in combination like diffusion tensor imaging,and neurite orientation dispersion and density imaging have proved effective in characterizing early parameters associated to alteration in water diffusion exchange within intracellular and extracellular compartments in brain white and grey matter.Thus,the combination of diffusion MRI imaging techniques and more complex neuropathological analysis could accelerate the discovery of new imaging biomarkers and the early diagnosis and neuromonitoring of patients affected with HD.

关键词： brain repair diffusion tensor imaging Huntington's disease neurite orientation dispersion and density imaging neuroconnectivity neuroinflammation neuroplasticity neuroregeneration R6/1 mice ultra-high field diffusion MRI

How mind-body therapies might reduce pathological features of Alzheimer’s disease

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Neural Regeneration Research 2022年第8期17卷 1757-1758页

作者： Melanie Hüttenrauch Susana Castro-Obregón División de Neurociencias Instituto de Fisiología CelularUniversidad Nacional Autónoma de México(UNAM)Circuito Exterior SNCiudad UniversitariaCDMXMexico

Alzheimer’s disease(AD)is an irreversible neurodegenerat i ve disorder that i s responsible for around 60-80%of all dementia cases and currently affects around 50 million people worldwide.As the population’s life span tends to increase,current predictions suggest that by 2050,152 million people worldwide will suffer from dementia(Balsinha,2019).While the exact cause of AD remains obscure,various hypotheses regarding AD etiology have been described in the last decades.According to the amyloid hypothesis,the pathogenic changes related to AD start with the accumulation of amyloid-beta(Aβ)in the brain.These Aβpeptides form oligomers and insoluble amyloid plaques which are neurotoxic and trigger harmful downstream events such as the aggregation of the microtubule-associated protein Tau into neurofibrillary tangles,chronic inflammation,and brain atrophy.

关键词： Alzheimer inflammation irreversible

Random noise stimulation in the treatment of patients with neurological disorders

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Neural Regeneration Research 2022年第12期17卷 2557-2562页

作者： Mateo A.Herrera-Murillo Mario Treviño Elias Manjarrez Facultad de Medicina Plan de Estudios Combinados en Medicina(PECEM)UNAMCircuito InteriorCiudad UniversitariaAv.UniversidadCiudad de MéxicoMéxico instituto de Neurociencias Universidad de GuadalajaraGuadalajaraJaliscoMéxico Instituto de Fisiología Benemérita Universidad Autónoma de PueblaPueblaMéxico

Random noise stimulation technique involves applying any form of energy(for instance,light,mechanical,electrical,sound)with unpredictable intensities through time to the brain or sensory receptors to enhance sensory,motor,or cognitive functions.Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli,but electrical energies applied to the brain or the skin are becoming more frequent,with a series of clinical applications.Indeed,recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability,improve cognitive/motor performance,and produce beneficial aftereffects at the behavioral and psychological levels.Here,we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders,including attention deficit hyperactivity disorder,schizophrenia,amblyopia,myopia,tinnitus,multiple sclerosis,post-stroke,vestibular-postural disorders,and sensitivity loss.Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects.In addition,we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.

关键词： auditory noise mechanical noise neurological disorders neuronal noise noise galvanic vestibular stimulation non-invasive brain stimulation transcranial electrical stimulation transcranial random noise stimulation

Targeting epidermal growth factor receptor signaling to facilitate cortical injury repair?

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Neural Regeneration Research 2024年第5期19卷 935-936页

作者： Ricardo Gómez-Oliva Pedro Nunez-Abades Carmen Castro Área de fisiología Facultad de Medicina Universidad de CádizCadizSpain instituto de Investigación e Innovación en Biomedicina de Cádiz CadizSpain departamento de fisiología Facultad de FarmaciaUniversidad de SevillaSevilleSpain

The existence of neural stem cells(NSC)in specific areas of the adult mammalian brain leads to the generation of new neurons involved in homeostatic mechanisms.This is the case of the NSC of the subventricular zone(SVZ)that produces olfactory bulb(OB)neurons.These neurons integrate into circuits to modulate sensory information and participate in olfactory processing(Bragado Alonso et al.,2019).A series of hierarchical events need to take place to produce OB neurons from NSC of the SVZ.First,the activation of quiescent NSC is necessary to produce intermediate transit amplifying progenitors(TAP),which will generate neuroblasts.The latter are cells that maintain a proliferative phenotype while in an immature phase.However,once they initiate migration toward the OB,they progressively undergo their differentiation into neurons(Kjell et al.,2020).

关键词： ventricular maintain

Glial cells in the center of future ischemic stroke treatments

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Neural Regeneration Research 2022年第12期17卷 2659-2660页

作者： IvóH.Hernández Maria JoséPérez-Álvarez Genomic Instability Group Spanish National Cancer Research Centre(CNIO)MadridSpain departamento de Biología(fisiología Animal)Facultad de Ciencias Universidad Autónoma de Madridand Instituto de Biología Molecular-CBMSOUAM/CSICMadridSpain

In the last century,increasing knowledge about glial cells has revealed their importance in brain physiology and disease and an exciting potential target for new therapeutic interventions(Hernández et al.,2021).Ischemic stroke is the most common of all types of stroke.As the second leading cause of disability and mortality,ischemic stroke is a serious socio-economic burden worldwide.Although it has been strongly associated with aging,during 2020 COVID-19 emerged as a new risk factor for ischemic stroke in younger patients(Cagnazzo et al.,2021).The only therapy or intervention currently available for humans is early reperfusion after the onset of the first symptoms.However,due to the high risk of brain hemorrhage,these treatments are suitable for only a small percentage of patients.Moreover,reperfusion does not prevent post-injury neurodegeneration,hence the importance of finding new therapeutic alternatives to ameliorate ischemic damage and improve post-stroke quality of life.

关键词： mortality treatment younger

Historical perspective of cell transplantation in Parkinson's disease

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World Journal of Transplantation 2017年第3期7卷 179-192页

作者： Alejandra Boronat-García Magdalena Guerra-Crespo René Drucker-Colín departamento de Neuropatología Molecular Instituto de Fisiología CelularUniversidad Nacional Autónoma de México

Cell grafting has been considered a therapeutic approach for Parkinson's disease(PD) since the 1980 s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of celltransplantation for PD consists in grafting dopamineproducing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.

关键词： Parkinson’s disease Cell replacement Animal models Nigrostriatal pathway Striatum Dopaminergic loss

Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer

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World Journal of Clinical Oncology 2018年第4期9卷 60-70页

作者： Angeles C Tecalco-Cruz Josué O Ramírez-Jarquín Programa de Investigación de Cáncer de Mama (PICM) Departamento de Biología Molecular y Biotec-nología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Instituto de Fisiología Celular Universidad Nacional Autónoma de México

Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.

关键词： Estrogen receptor alpha polyubiquitination Breast cancer Estrogen receptor alpha