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Kazumi Yoshizawa, Narumaki Arai, Yukina Suzuki, Toka Nakamura, Kota Takeuchi, Reinii Sakamoto, Ritsuko Masuda
An important role of voltage-gated sodium channels (VGSCs) in many different pain states has been established in animal models and humans wherein sodium channel blockers partially ameliorate pain. However, behavioral tests for screening analgesics that exhibit pharmacologic action by acting on VGSCs are rarely reported, and there are no studies on antinociception using veratrine as a nociceptive agent. The aim of the present study was to examine the amount of nociceptive behavior evoked by subcutaneous administration of veratrine into the hindpaw and investigate whether veratrine can be used as a VGSC agonist to test the pharmacological properties of candidate analgesics via sodium channel blockade...
July 11, 2018: Synapse
Neil C Lax, Stacy-Ann J Parker, Edward J Hilton, Youstina Seliman, Kevin J Tidgewell, Benedict J Kolber
Marine cyanobacteria represent a unique source in the field of drug discovery due to the secondary metabolites they produce and the structural similarity these compounds have to endogenous mammalian receptor ligands. A series of cyanobacteria were subjected to extraction, fractionation by column chromatography and screened for affinity against CNS targets with a focus on serotonin receptors (5-HT). Out of 276 fractions screened, 21% had activity at 5-HT receptors and/or the 5-HT transporter. One sample, a cyanobacterium identified by 16S rRNA sequencing as Leptolyngbya from Las Perlas archipelago in Panama, contained a fraction with noted affinity for the 5-HT7 receptor (5-HT7 R)...
July 10, 2018: Synapse
John Hamilton, Sabrina Swenson, Andras Hajnal, Panayotis K Thanos
Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to 4 groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed...
July 10, 2018: Synapse
Anne E Homan, Stephen D Meriney
The impact of presynaptic transmitter release site organization on synaptic function has been a vibrant area of research for synaptic physiologists. Because there is a highly nonlinear relationship between presynaptic calcium influx and subsequent neurotransmitter release at synapses, the organization and density of calcium sources (voltage gated calcium channels; VGCCs) relative to calcium sensors located on synaptic vesicles is predicted to play a major role in shaping the dynamics of neurotransmitter release at a synapse...
June 29, 2018: Synapse
Kelly Smart, Sylvia M L Cox, Atsuko Nagano-Saito, Pedro Rosa-Neto, Marco Leyton, Chawki Benkelfat
BACKGROUND: [11 C]ABP688 is a positron emission tomography (PET) radioligand that binds selectively to metabotropic glutamate type 5 receptors (mGluR5). The use of this tracer has identified receptor binding changes in clinical populations, and has been informative in drug occupancy studies. However, previous studies have found significant increases in [11 C]ABP688 binding in the later scan of same-day comparisons, and estimates of test-retest reliability under consistent scanning conditions are not available...
June 23, 2018: Synapse
Jeffrey M Miller, Francesca Zanderigo, Priya D Purushothaman, Christine DeLorenzo, Harry Rubin-Falcone, R Todd Ogden, John Keilp, Maria A Oquendo, Nabeel Nabulsi, Yiyun H Huang, Ramin V Parsey, Richard E Carson, J John Mann
Endogenous kappa opioids mediate pathological responses to stress in animal models. However, the relationship of the kappa opioid receptor (KOR) to life stress and to psychopathology in humans is not well described. This pilot study sought, for the first time, to quantify KOR in major depressive disorder (MDD) in vivo in humans using PET imaging. KOR binding was quantified in vivo by PET imaging with the [11 C]GR103545 radiotracer in 13 healthy volunteers and 10 participants with current MDD. We examined the relationship between regional [11 C]GR103545 total volume of distribution (VT ) and diagnosis, childhood trauma, recent life stress, and, in a subsample, salivary cortisol levels during a modified Trier Social Stress Test (mTSST), amygdala, hippocampus, ventral striatum and raphe nuclei...
June 23, 2018: Synapse
Mahendra Singh, Brendan Lujan, Robert Renden
Synaptic vesicle exocytosis is intimately dependent on free local Ca2+ near active zones. Genetically-encoded calcium indicators (GECIs) have become an indispensable tool to monitor calcium dynamics during physiological responses, and they are widely used as a proxy to monitor activity in neuronal ensembles and at synaptic terminals. However, GECIs' ability to bind Ca2+ at physiologically-relevant concentration makes them strong candidates to affect calcium homeostasis and alter synaptic transmission by exogenously increasing Ca2+ buffering...
June 23, 2018: Synapse
Yong Kee Choi, Frank I Tarazi
The atypical antipsychotic drug iloperidone has high affinity for a wide range of neurotransmitter receptors including dopaminergic (DA), serotonergic and adrenergic receptors. We examined the long-term effects of multiple doses of iloperidone on DA D1 , D2 , D3 and D4 receptor subtypes. Sprague-Dawley adult rats (n=8/group) received daily intraperitoneal injections of iloperiodone (0.5, 1, or 5 mg/kg) or vehicle for 4 weeks. Receptor autoradiography quantified the levels of DA receptors in medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP)...
June 23, 2018: Synapse
Joshua Gertler, Savannah Tollefson, Rehima Jordan, Michael L Himes, N Scott Mason, W Gordon Frankle, Rajesh Narendran
Studies in nonhuman primates and humans have demonstrated that amphetamine-induced dopamine release in the cortex can be measured with [11 C]FLB 457 and PET imaging. This technique has been successfully used in recent clinical studies to show decreased dopamine transmission in the prefrontal cortex in schizophrenia and alcohol dependence. Here, we present data from a cohort of twelve healthy controls in whom an oral amphetamine challenge (0.5 mg kg-1 ) did not lead to a significant reduction in [11 C]FLB 457 BPND (i...
June 6, 2018: Synapse
Onarae V Rice, Charles R Ashby, Clark Dixon, William Laurenzo, Jason Hayden, Rui Song, Jin Li, Amit K Tiwari, Eliot L Gardner
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric syndrome that occurs in individuals exposed to extremely threatening or traumatic events. In both animals and humans, dopamine (DA) function appears to be dysregulated in brain areas involved in the conditioned fear response(s) that underlie PTSD. In this study, we determined the effect of the selective DA D3 receptor antagonists YQA14A (6.25, 12.5 and 25 mg/kg i.p.) and SB-277011A (6 mg/kg i.p.) on tone-induced fear (assessed by measuring freeze time) in a modified version of the single-prolonged stress (SPS) model of PTSD in adult male Sprague-Dawley rats...
April 27, 2018: Synapse
Elizabeth Monserrat Hernández-Hernández, Karen Caporal Hernandez, Rubén Antonio Vázquez-Roque, Alfonso Díaz, Fidel de la Cruz, Benjamin Florán, Gonzalo Flores
Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats...
August 2018: Synapse
Yi-Wen Chen, Ada Akad, Ruka Aderogba, Tara G Chowdhury, Chiye Aoki
Adolescence is accompanied by increased vulnerability to psychiatric illnesses, including anxiety, depression, schizophrenia, and eating disorders. The hippocampus is important for regulating emotional state through its ventral compartment and spatial cognition through its dorsal compartment. Previous animal studies have examined hippocampal development at stages before, after or at single time points during adolescence. However, only one study has investigated morphological changes at multiple time points during adolescence, and no study has yet compared developmental changes of dorsal versus ventral hippocampi...
July 2018: Synapse
Inki Lee, Jin Su Kim, Joon Yeun Park, Byung Hyun Byun, Su Yeon Park, Joon Ho Choi, Hansol Moon, Jung Young Kim, Kyo Chul Lee, Dae Yoon Chi, Kyeong Min Kim, Ilhan Lim, Joo Hyun Kang, Soon Hyuk Ahn, Byung Il Kim, Jeong Ho Ha, Sang Moo Lim
123 I-FP-CIT and 18 F-FP-CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head-to-head comparisons between 123 I-FP-CIT and 18 F-FP-CIT. Therefore, in this study, 123 I-FP-CIT SPECT/CT was compared with 18 F-FP-CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT...
July 2018: Synapse
Juan David Olivares-Hernández, Fabio García-García, Israel Camacho-Abrego, Gonzalo Flores, Enrique Juárez-Aguilar
A growing body of evidence suggests that growth hormone (GH) affects synaptic plasticity at both the molecular and electrophysiological levels. However, unclear is whether plasticity that is stimulated by GH is associated with changes in neuron structure. This study investigated the effect of intracerebroventricular (ICV) administration of GH on the morphology of pyramidal neurons of the CA1 region of the dorsal hippocampus and layer III of the prefrontal cortex. Male Wistar rats received daily ICV injections of GH (120 ng) for 7 days, and they were euthanized 21 days later...
July 2018: Synapse
John Hamilton, Matthew Marion, Antonio Figueiredo, Brendan H Clavin, Dale Deutsch, Martin Kaczocha, Samir Haj-Dahmane, Panayotis K Thanos
Genetic and pharmacological manipulation of endocannabinoid (eCB) signaling has previously been shown to have an important role on the rewarding properties of drugs of abuse, including cocaine. Recently, fatty acid binding proteins (FABPs) have been proposed as intracellular transporters of the endocannabinoid anandamide (AEA) as well as other bioactive lipids to their catabolic enzyme, fatty acid amide hydrolase (FAAH). The role of these transporters in modulating the brains reward system has yet to be investigated...
June 2018: Synapse
Arturo Avendaño-Estrada, Miguel Angel Ávila-Rodríguez
Dopaminergic PET imaging is a useful tool to assess the dopaminergic integrity and to follow-up longitudinal studies. The aim of this study was to evaluate the reliability and reproducibility of different reference tissue-based methods to determine the non-displaceable binding potential (BPND ) as a quantitative measure of 11 C-DTBZ binding to the VMAT2 in rat striatum using cerebellum as reference region. Eight healthy Wistar rats underwent two microPET scans at the age of 12 (test) and 20 weeks (retest). BPND was determined using the simplified reference tissue model, Logan reference tissue model, and multilinear reference tissue models (MRTMo and MRTM2)...
June 2018: Synapse
Adriana B Silva-Gómez, Dolores A Bravo-Duran, Jose R Eguibar, Carmen Cortes
Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant...
June 2018: Synapse
Mikhail Y Lipin, Jozsef Vigh
Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔVm ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina...
May 2018: Synapse
Adeline Orts-Del'Immagine, Jason R Pugh
Parallel fiber synapses in the cerebellum express a wide range of presynaptic receptors. However, presynaptic receptor expression at individual parallel fiber synapses is quite heterogeneous, suggesting physiological mechanisms regulate presynaptic receptor expression. We investigated changes in presynaptic GABAB receptors at parallel fiber-stellate cell synapses in acute cerebellar slices from juvenile mice. GABAB receptor-mediated inhibition of excitatory postsynaptic currents (EPSCs) is remarkably diverse at these synapses, with transmitter release at some synapses inhibited by >50% and little or no inhibition at others...
May 2018: Synapse
Mohammadmehdi Hadipour, Gholamreza Kaka, Farideh Bahrami, Gholam Hossein Meftahi, Gila Pirzad Jahromi, Alireza Mohammadi, Hedayat Sahraei
Extracellular beta-amyloid (Aβ) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aβ models of the AD...
May 2018: Synapse
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