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Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics

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https://www.readbyqxmd.com/read/28653282/therapeutic-targets-for-multiple-sclerosis-current-treatment-goals-and-future-directions
#1
REVIEW
Andrew L Smith, Jeffrey A Cohen, Le H Hua
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing-remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653281/fingolimod-exerts-only-temporary-antiepileptogenic-effects-but-longer-lasting-positive-effects-on-behavior-in-the-wag-rij-rat-absence-epilepsy-model
#2
Antonio Leo, Rita Citraro, Nicola Amodio, Caterina De Sarro, Maria Eugenia Gallo Cantafio, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#3
REVIEW
Frederick C Nucifora, Marina Mihaljevic, Brian J Lee, Akira Sawa
Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653279/chronic-paroxetine-treatment-prevents-the-emergence-of-abnormal-electroencephalogram-oscillations-in-huntington-s-disease-mice
#4
Sandor Kantor, Janos Varga, Shreya Kulkarni, A Jennifer Morton
Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington's disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg)...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653278/evidence-based-psychotherapy-advantages-and-challenges
#5
REVIEW
Sarah C Cook, Ann C Schwartz, Nadine J Kaslow
Evidence-based psychotherapies have been shown to be efficacious and cost-effective for a wide range of psychiatric conditions. Psychiatric disorders are prevalent worldwide and associated with high rates of disease burden, as well as elevated rates of co-occurrence with medical disorders, which has led to an increased focus on the need for evidence-based psychotherapies. This chapter focuses on the current state of evidence-based psychotherapy. The strengths and challenges of evidence-based psychotherapy are discussed, as well as misperceptions regarding the approach that may discourage and limit its use...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28653277/moving-beyond-serendipity-to-mechanism-driven-psychiatric-therapeutics
#6
EDITORIAL
Andrew A Pieper, Jay M Baraban
No abstract text is available yet for this article.
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28639153/genomics-of-lithium-action-and-response
#7
REVIEW
Benjamin S Pickard
Lithium is the most successful mood stabilizer treatment for bipolar disorder. However, unlike conventional drugs that are designed to interact with a specific molecular target, the actions of lithium are distributed across many biological processes and pathways. Treatment response is subject to genetic variation between individuals and similar genetic variation may dictate susceptibility to side effects. Transcriptomic, genomic, and cell-model research strategies have all been deployed in the search for the genetic factors and biological systems that mediate the interaction between genetics and the therapeutic actions of lithium...
June 21, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28631082/abstracts-from-the-asent-19th-annual-meeting
#8
(no author information available yet)
No abstract text is available yet for this article.
June 19, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28612328/antidepressant-actions-of-ketamine-mediated-by-the-mechanistic-target-of-rapamycin-nitric-oxide-and-rheb
#9
REVIEW
Maged M Harraz, Solomon H Snyder
The weeks/months it takes for traditional antidepressants to act pose an obstacle in the management of depression. Ketamine's prompt and sustained antidepressant effects constitute a major advance. Multiple studies implicate glutamatergic signaling to protein synthesis machinery and synapse formation in ketamine's antidepressant effects. Here we review evidence linking ketamine to glutamate receptor subtypes and protein homeostasis. We describe a signaling cascade wherein nitric oxide drives the formation of a ternary protein complex comprised of glyceraldehyde 3-phosphate dehydrogenase, seven in absentia homolog 1, and Ras homolog enriched in brain downstream of the glutamate N-methyl-D-aspartate receptor...
June 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28608171/genetic-approaches-to-understanding-psychiatric-disease
#10
REVIEW
Jacob J Michaelson
Human genetic studies have been the driving force in bringing to light the underlying biology of psychiatric conditions. As these studies fill in the gaps in our knowledge of the mechanisms at play, we will be better equipped to design therapies in rational and targeted ways, or repurpose existing therapies in previously unanticipated ways. This review is intended for those unfamiliar with psychiatric genetics as a field and provides a primer on different modes of genetic variation, the technologies currently used to probe them, and concepts that provide context for interpreting the gene-phenotype relationship...
June 12, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28593439/clinical-and-histopathological-amelioration-of-experimental-autoimmune-encephalomyelitis-by-aav-vectors-expressing-a-soluble-interleukin-23-receptor
#11
Marta Miralles, Herena Eixarch, Marcos Tejero, Carme Costa, Keiji Hirota, A Raul Castaño, Meritxell Puig, Gitta Stockinger, Xavier Montalban, Assumpció Bosch, Carmen Espejo, Miguel Chillon
The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors...
June 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28585223/a-molecular-tweezer-ameliorates-motor-deficits-in-mice-overexpressing-%C3%AE-synuclein
#12
Franziska Richter, Sudhakar R Subramaniam, Iddo Magen, Patrick Lee, Jane Hayes, Aida Attar, Chunni Zhu, Nicholas R Franich, Nicholas Bove, Krystal De La Rosa, Jacky Kwong, Frank-Gerrit Klärner, Thomas Schrader, Marie-Françoise Chesselet, Gal Bitan
Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies. Accordingly, therapeutic approaches targeting the toxic α-synuclein assemblies are attractive for these incurable disorders...
June 5, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28585222/potential-therapeutic-effects-of-psilocybin
#13
REVIEW
Matthew W Johnson, Roland R Griffiths
Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research...
June 5, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28585221/vagal-nerve-stimulation-for-treatment-resistant-depression
#14
REVIEW
Flavia R Carreno, Alan Frazer
Major depressive disorder (MDD) is prevalent. Although standards antidepressants are more effective than placebo, up to 35% of patients do not respond to 4 or more conventional treatments and are considered to have treatment-resistant depression (TRD). Considerable effort has been devoted to trying to find effective treatments for TRD. This review focuses on vagus nerve stimulation (VNS), approved for TRD in 2005 by the Food and Drugs Administration. Stimulation is carried by bipolar electrodes on the left cervical vagus nerve, which are attached to an implanted stimulator generator...
June 5, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28560710/hcn-channel-targets-for-novel-antidepressant-treatment
#15
REVIEW
Stacy M Ku, Ming-Hu Han
Major depressive disorder (MDD) is a chronic and potentially life threatening illness that carries a staggering global burden. Characterized by depressed mood, MDD is often difficult to diagnose and treat owing to heterogeneity of syndrome and complex etiology. Contemporary antidepressant treatments are based on improved monoamine-based formulations from serendipitous discoveries made > 60 years ago. Novel antidepressant treatments are necessary, as roughly half of patients using available antidepressants do not see long-term remission of depressive symptoms...
May 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28560709/targeting-neural-hyperactivity-as-a-treatment-to-stem-progression-of-late-onset-alzheimer-s-disease
#16
REVIEW
Rebecca P Haberman, Audrey Branch, Michela Gallagher
Sporadic late-onset Alzheimer's disease (LOAD), the most common form of dementia in the elderly, causes progressive and severe loss of cognitive abilities. With greater numbers of people living to advanced ages, LOAD will increasingly burden both the healthcare system and society. There are currently no available disease-modifying therapies, and the failure of several recent pathology-based strategies has highlighted the urgent need for effective therapeutic targets. With aging as the greatest risk factor for LOAD, targeting mechanisms by which aging contributes to disease could prove an effective strategy to delay progression to clinical dementia by intervention in elderly individuals in an early prodromal stage of disease...
May 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28560708/tonabersat-prevents-inflammatory-damage-in-the-central-nervous-system-by-blocking-connexin43-hemichannels
#17
Yeri Kim, Jarred M Griffin, Mohd N Mat Nor, Jie Zhang, Peter S Freestone, Helen V Danesh-Meyer, Ilva D Rupenthal, Monica Acosta, Louise F B Nicholson, Simon J O'Carroll, Colin R Green
The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion...
May 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28547702/emerging-treatments-in-eating-disorders
#18
REVIEW
Michael Lutter
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments...
May 25, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28536851/targeting-adult-neurogenesis-to-optimize-hippocampal-circuits-in-aging
#19
REVIEW
Kathleen M McAvoy, Amar Sahay
Millions of individuals suffer from age-related cognitive decline, defined by impaired memory precision. Increased understanding of hippocampal circuit mechanisms underlying memory formation suggests a role for computational processes such as pattern separation and pattern completion in memory precision. We describe evidence implicating the dentate gyrus-CA3 circuit in pattern separation and completion, and examine alterations in dentate gyrus-CA3 circuit structure and function with aging. We discuss the role of adult hippocampal neurogenesis in memory precision in adulthood and aging, as well as the circuit mechanisms underlying the integration and encoding functions of adult-born dentate granule cells...
May 23, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28536850/effectiveness-of-daily-prednisolone-to-slow-progression-of-human-t-lymphotropic-virus-type-1-associated-myelopathy-tropical-spastic-paraparesis-a-multicenter-retrospective-cohort-study
#20
Ariella L G Coler-Reilly, Tomoo Sato, Toshio Matsuzaki, Masanori Nakagawa, Masaaki Niino, Masahiro Nagai, Tatsufumi Nakamura, Norihiro Takenouchi, Natsumi Araya, Naoko Yagishita, Eisuke Inoue, Yoshihisa Yamano
Millions of people are infected with human T-lymphotropic virus type 1 (HTLV-1) worldwide; notable endemic areas include Brazil, the Caribbean islands, Iran, and Japan. A small number of those infected develop the progressive neurodegenerative disease HTLV-1-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP), which is characterized by chronic spinal cord inflammation and accompanying myelopathic symptoms. The corticosteroid prednisolone (PSL) is a classic treatment for HAM/TSP, yet its effectiveness remains controversial owing to insufficient and conflicting studies...
May 23, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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