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https://www.readbyqxmd.com/read/29047301/pimavanserin-novel-pharmacotherapy-for-parkinson-s-disease-psychosis
#1
Zeyad T Sahli, Frank I Tarazi
Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the preclinical discovery of pimavanserin. It analyzes the pharmacological, behavioral and molecular mechanisms of pimavanserin and their contribution to the therapeutic advantages of the drug as reported in published preclinical and clinical studies, and product labels. Expert opinion: Pimavanserin exhibits a unique pharmacological profile with nanomolar affinity at serotonin 5-HT2A and 5-HT2C receptors...
October 19, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29043468/cognitive-and-behavioral-disorders-in-parkinson-s-disease-an-update-i-cognitive-impairments
#2
Costanza Papagno, Luigi Trojano
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, a growing body of evidence demonstrated that PD encompasses several non-motor disturbances as well, such as cognitive impairment. Cognitive defects can be present since early stages of the disease but tend to dominate the clinical picture as the disease progresses. Around 40% of patients with PD present with cognitive impairments in several cognitive domains including attention, working memory and executive functions, language, visuospatial skills, and episodic memory; in later stages of the disease, cognitive defects and associated behavioral disorders concur to determine clinically relevant PD-associated dementia...
October 17, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29038583/zdhhc13-dependent-drp1-s-palmitoylation-impacts-brain-bioenergetics-anxiety-coordination-and-motor-skills
#3
Eleonora Napoli, Gyu Song, Siming Liu, Alexsandra Espejo, Carlos J Perez, Fernando Benavides, Cecilia Giulivi
Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn(2+)-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29035044/nicotine-alters-the-gut-microbiome-and-metabolites-of-gut-brain-interactions-in-a-sex-specific-manner
#4
Liang Chi, Ridwan Mahbub, Bei Gao, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, Kun Lu
As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Sex is an important factor that shapes the gut microbiome, but the role of sex in the interaction among nicotine, gut bacteria, and related metabolites remains unknown...
October 16, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29033975/a-hypothesis-and-review-of-the-relationship-between-selection-for-improved-production-efficiency-coping-behavior-and-domestication
#5
Wendy M Rauw, Anna K Johnson, Luis Gomez-Raya, Jack C M Dekkers
Coping styles in response to stressors have been described both in humans and in other animal species. Because coping styles are directly related to individual fitness they are part of the life history strategy. Behavioral styles trade off with other life-history traits through the acquisition and allocation of resources. Domestication and subsequent artificial selection for production traits specifically focused on selection of individuals with energy sparing mechanisms for non-production traits. Domestication resulted in animals with low levels of aggression and activity, and a low hypothalamic-pituitary-adrenal (HPA) axis reactivity...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29032922/serotonin-transporter-density-in-binge-eating-disorder-and-pathological-gambling-a-pet-study-with-11-c-madam
#6
Joonas Majuri, Juho Joutsa, Jarkko Johansson, Valerie Voon, Riitta Parkkola, Hannu Alho, Eveliina Arponen, Valtteri Kaasinen
Behavioral addictions, such as pathological gambling (PG) and binge eating disorder (BED), appear to be associated with specific changes in brain dopamine and opioid function, but the role of other neurotransmitter systems is less clear. Given the crucial role of serotonin in a number of psychiatric disorders, we aimed to compare brain serotonergic function among individuals with BED, PG and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls were scanned with high-resolution positron emission tomography (PET) using the serotonin transporter (SERT) tracer [(11)C]MADAM...
October 9, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29028935/latent-profile-analysis-reveals-behavioral-and-brain-correlates-of-dopamine-cognition-associations
#7
Martin Lövdén, Nina Karalija, Micael Andersson, Anders Wåhlin, Jan Axelsson, Ylva Köhncke, Lars S Jonasson, Anna Rieckman, Goran Papenberg, Douglas D Garrett, Marc Guitart-Masip, Alireza Salami, Katrine Riklund, Lars Bäckman, Lars Nyberg, Ulman Lindenberger
Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with 11C-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed)...
September 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29028150/potential-of-micrornas-as-novel-targets-in-the-alleviation-of-pathological-fear
#8
REVIEW
Conor P Murphy, Nicolas Singewald
The current treatment of post-traumatic stress disorder (PTSD), phobias and other anxiety disorders, remains insufficient particularly in producing long-lasting full symptom control. Dysfunctional fear processing is common in these disorders, including a deficiency in fear-inhibitory mechanisms and impairment in the ability to discriminate between safety and danger cues. Research has aimed to elucidate brain circuitries, neurotransmitters and downstream signaling pathways important in the alleviation of aberrant fear, with a specific focus on mechanisms modulating fear memory and its behavioral expression...
October 13, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29027614/statistical-crossover-and-nonextensive-behavior-of-neuronal-short-term-depression
#9
A J da Silva, S Floquet, D O C Santos
The theoretical basis of neuronal coding, associated with short-term degradation in synaptic transmission, is a matter of debate in the literature. In fact, electrophysiological signals are commonly characterized as inversely proportional to stimulus intensity. Among theoretical descriptions of this phenomenon, models based on 1/f-dependency are employed to investigate the biophysical properties of short-term synaptic depression. In this work, we formulate a model based on a paradigmatic q-differential equation to obtain a generalized formalism useful for investigation of nonextensivity in this specific type of synaptic plasticity...
October 13, 2017: Journal of Biological Physics
https://www.readbyqxmd.com/read/29027462/dual-signal-microbial-biosensor-for-the-detection-of-dopamine-without-inference-from-other-catecholamine-neurotransmitters
#10
Yu-Kuan Lin, Yi-Chun Yeh
Dopamine, one of catecholamine neurotransmitters, plays an important role in many brain functions and behavioral responses. In this study, we developed a novel dual-signal whole-cell biosensor for the detection of dopamine through the generation of red fluorescent proteins and 6-decarboxylated betaxanthin pigments. The proposed system responses specifically to dopamine with a detection limit of 1.43 μM. Furthermore, a combination of dual output signals makes it possible to reduce the interference from other catecholamine neurotransmitters, including L-DOPA, epinephrine, and norepinephrine...
October 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29027157/animal-models-for-bipolar-disorder-from-bedside-to-the-cage
#11
REVIEW
Dominik K E Beyer, Nadja Freund
Bipolar disorder is characterized by recurrent manic and depressive episodes. Patients suffering from this disorder experience dramatic mood swings with a wide variety of typical behavioral facets, affecting overall activity, energy, sexual behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased risk for suicide. Effective treatment options are limited and diagnosis can be complicated. To overcome these obstacles, a better understanding of the neurobiology underlying bipolar disorder is needed...
October 13, 2017: International Journal of Bipolar Disorders
https://www.readbyqxmd.com/read/29024786/neurobiological-correlates-of-pain-avoidance-like-behavior-in-morphine-dependent-and-non-dependent-rats
#12
Amanda R Pahng, Rod I Paulsen, M Adrienne McGinn, Kimberly N Edwards, Scott Edwards
Repeated use of opioids can lead to the development of analgesic tolerance and dependence. Additionally, chronic opioid exposure can cause a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may drive continued or escalated use of opioids to manage worsening pain symptoms. Opioid-induced hyperalgesia has traditionally been measured in rodents via reflex-based assays, including the von Frey method. To better model the cognitive/motivational dimension of pain in a state of opioid dependence and withdrawal, we employed a recently developed non-reflex-based method for measuring pain avoidance-like behavior in animals (mechanical conflict avoidance test)...
October 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29023380/the-gut-microbiome-feelings-of-the-brain-a-perspective-for-non-microbiologists
#13
REVIEW
Aaron Lerner, Sandra Neidhöfer, Torsten Matthias
Objectives: To comprehensively review the scientific knowledge on the gut-brain axis. Methods: Various publications on the gut-brain axis, until 31 July 2017, were screened using the Medline, Google, and Cochrane Library databases. The search was performed using the following keywords: "gut-brain axis", "gut-microbiota-brain axis", "nutrition microbiome/microbiota", "enteric nervous system", "enteric glial cells/network", "gut-brain pathways", "microbiome immune system", "microbiome neuroendocrine system" and "intestinal/gut/enteric neuropeptides"...
October 12, 2017: Microorganisms
https://www.readbyqxmd.com/read/29021837/the-bssg-rat-model-of-parkinson-s-disease-progressing-towards-a-valid-predictive-model-of-disease
#14
REVIEW
Jackalina M Van Kampen, Harold A Robertson
ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder, classically considered a movement disorder. A great deal is known about the anatomical connections and neuropathology and pharmacological changes of PD, as they relate to the loss of dopaminergic function and the appearance of cardinal motor symptoms. Our understanding of the role of dopamine in PD has led to the development of effective pharmacological treatments of the motor symptoms in the form of dopamine replacement therapy using levodopa and dopaminergic agonists...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29020418/striatal-n-acetylaspartate-synthetase-shati-nat8l-regulates-depression-like-behaviors-via-mglur3-mediated-serotonergic-suppression-in-mice
#15
Yoshiaki Miyamoto, Noriyuki Iegaki, Kequan Fu, Yudai Ishikawa, Kazuyuki Sumi, Sota Azuma, Kyosuke Uno, Shin-Ichi Muramatsu, Atsumi Nitta
Background: Several clinical studies have suggested that N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes NAA from L-aspartate and acetyl-coenzyme A. Further, NAA is converted into NAAG, a neurotransmitter for metabotropic glutamate receptor 3 (mGluR3)...
August 31, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29018212/enhanced-therapeutic-treatment-of-colorectal-cancer-using-surface-modified-nanoporous-acupuncture-needles
#16
Bo Ram Lee, Hye-Rim Kim, Eun-Sook Choi, Jung-Hoon Cho, Nam-Jun Kim, Jung-Hee Kim, Kyeong-Min Lee, Abdul Razzaq, Hansaem Choi, Yunju Hwang, Craig A Grimes, Bong-Hyo Lee, Eunjoo Kim, Su-Il In
Acupuncture originated within the auspices of Oriental medicine, and today is used as an alternative method for treating various diseases and symptoms. The physiological mechanisms of acupuncture appear to involve the release of endogenous opiates and neurotransmitters, with the signals mediating through electrical stimulation of the central nervous system (CNS). Earlier we reported a nanoporous stainless steel acupuncture needle with enhanced therapeutic properties, evaluated by electrophysiological and behavioral responses in Sprague-Dawley (SD) rats...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29017573/gad67-haploinsufficiency-reduces-amyloid-pathology-and-rescues-olfactory-memory-deficits-in-a-mouse-model-of-alzheimer-s-disease
#17
Yue Wang, Zheng Wu, Yu-Ting Bai, Gang-Yi Wu, Gong Chen
BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia...
October 10, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29016795/leonurine-exerts-antidepressant-like-effects-in-the-chronic-mild-stress-induced-depression-model-in-mice-by-inhibiting-neuroinflammation
#18
Miaomiao Jia, Chenxin Li, Ying Zheng, Xiaojing Ding, Meng Chen, Jianhua Ding, Renhong Du, Ming Lu, Gang Hu
Background: Leonurine is an active alkaloid that is extracted from Traditional Chinese Medicine Herba leonuri. Emerging evidence indicates that leonurine produces neuroprotective effects in ischemic stroke, Parkinson's disease, and Alzheimer's disease. However, the effect of leonurine in neuropsychiatric disorders, especially in major depression, remains unknown. Methods: We used the chronic mild stress mouse model to explore the antidepressant effects of leonurine and the potential mechanisms...
July 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28993890/resting-gaba-concentration-predicts-inhibitory-control-during-an-auditory-go-nogo-task
#19
Chia-Hsiung Cheng, David M Niddam, Shih-Chieh Hsu, Chia-Yih Liu, Shang-Yueh Tsai
Inhibitory control plays an important role in goal-directed behavior. Although substantial inter-individual variability exists in the behavioral performance of response inhibition, the corresponding modulating neurochemical and neurophysiological mechanisms remain unclear. Thus, the present study aimed to explore the relationship between behavioral response inhibition, GABA+ concentrations and automatic sensory gating (SG) in the auditory cortices. We recruited 19 healthy adults to undergo magnetoencephalography, magnetic resonance spectroscopy (MRS), and behavioral experiments...
October 9, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28992195/neural-versus-gonadal-gnih-are-they-independent-systems-a-mini-review
#20
George E Bentley, Kathryn Wilsterman, Darcy K Ernst, Sharon E Lynn, Molly J Dickens, Rebecca M Calisi, Lance J Kriegsfeld, Daniela Kaufer, Anna C Geraghty, Dax viviD, Nicolette L McGuire, Patricia C Lopes, Kazuyoshi Tsutsui
Based on research in protochordates and basal vertebrates, we know that communication across the first endocrine axes likely relied on diffusion. Because diffusion is relatively slow, rapid responses to some cues, including stress-related cues, may have required further local control of axis outputs (e.g., steroid hormone production by the gonads). Despite the evolution of much more efficient circulatory systems and complex nervous systems in vertebrates, production of many "neuro"transmitters has been identified outside of the hypothalamus across the vertebrate phylogeny and these neurotransmitters are known to locally regulate endocrine function...
September 2, 2017: Integrative and Comparative Biology
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