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Savannah Tollefson, Joshua Gertler, Michael L Himes, Jennifer Paris, Steve Kendro, Brian Lopresti, Scott N Mason, Rajesh Narendran
Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self-administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder ("cocaine users") compared to controls...
September 21, 2018: Synapse
Timothy D Folsom, LeeAnn Higgins, Todd W Markowski, Timothy J Griffin, S Hossein Fatemi
The fragile X mental retardation 1 knockout (Fmr1 KO) mouse replicates behavioral deficits associated with autism, fragile X syndrome, and schizophrenia. Less is known whether protein expression changes are consistent with findings in subjects with schizophrenia. In the current study we used liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics to determine the protein expression of four subcellular fractions in forebrains of Fmr1 KO mice vs. C57BL/6J mice and the effect of a negative allosteric modulator of mGluR5 - 2-Methyl-6-(phenylethynyl)pyridine (MPEP) - on protein expression...
September 3, 2018: Synapse
Ayako Kumagai, Tsutomu Sasaki, Kenta Matsuoka, Masayoshi Abe, Toshihide Tabata, Yumi Itoh, Hiroyuki Fuchino, Sartagul Wugangerile, Mika Suga, Tomoko Yamaguchi, Hidehisa Kawahara, Yasuo Nagaoka, Kenji Kawabata, Miho Kusuda Furue, Hiroshi Takemori
Dysfunction of mitochondrial activity is often associated with the onset and progress of neurodegenerative diseases. Membrane depolarization induced by Na+ influx increases intracellular Ca2+ levels in neurons, which upregulates mitochondrial activity. However, overlimit of Na+ influx and its prolonged retention ultimately cause excitotoxicity leading to neuronal cell death. To return the membrane potential to the normal level, Na+ /K+ -ATPase exchanges intracellular Na+ with extracellular K+ by consuming a large amount of ATP...
August 18, 2018: Synapse
Cesar Pinzón-Parra, Blanca Vidal-Jiménez, Israel Camacho-Abrego, Alejandra A Flores-Gómez, Antonio Rodríguez-Moreno, Gonzalo Flores
Little has been investigated about the effects of stress on synaptic communication at prepubertal age, a stage considered as juvenile. This period of development is related to socialization through play. Our group has studied the changes of neuronal morphology in limbic structures caused by stress at prenatal and at early postnatal ages (before weaning) in the rat. In the present study, we assessed the effect of restraint stress at juvenile ages. Male Sprague-Dawley rats from postnatal day (PD) 21 to PD35 were restrained (from movement) for 2 hrs...
August 13, 2018: Synapse
Jeong-Hee Kim, Paul Cumming, Young-Don Son, Hang-Keun Kim, Yo-Han Joo, Jong-Hoon Kim
In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlations of dopamine D2/3 receptor availability between striatal and extrastriatal regions using [18 F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis...
July 31, 2018: Synapse
Thea Pinholt Lillethorup, Andreas Nørgaard Glud, Natalie Landeck, Aage Kristian Olsen Alstrup, Steen Jakobsen, Kim Vang, Doris J Doudet, David J Brooks, Deniz Kirik, Rainer Hinz, Jens Christian Sørensen, Anne M Landau
Parkinson's disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson's disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11 C](R)PK11195, to image brain microglial activation and (+)-α-[11 C]dihydrotetrabenazine ([11 C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs)...
July 15, 2018: Synapse
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 hind paw 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-HTRs). Out of 276 fractions screened, 21% had activity at 5-HTRs and/or the 5-HT transporter (SERT). 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 four 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
Rodolfo Sánchez-Zavaleta, Hernán Cortés, José Arturo Avalos-Fuentes, Ubaldo García, José Segovia Vila, David Erlij, Benjamín Florán
Recent studies suggested the expression of CB2 receptors in neurons of the CNS, however, most of these studies have only explored one aspect of the receptors, i.e., expression of protein, messenger RNA, or functional response, and more complete studies appear to be needed to establish adequately their role in the neuronal function. Electron microscopy studies showed the presence of CB2r in asymmetric terminals of the substantia nigra pars reticulata (SNr), and its mRNA appeared is expressed in the subthalamic nucleus...
November 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...
November 2018: Synapse
Kelly Smart, Sylvia M L Cox, Atsuko Nagano-Saito, Pedro Rosa-Neto, Marco Leyton, Chawki Benkelfat
[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. The objective of this study was to assess the variability of [11 C]ABP688 binding in healthy people in scans performed at the same time of day...
September 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 positron emission tomography (PET). 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...
September 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...
September 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
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...
August 2018: Synapse
Vassilios Papaleonidopoulos, Stylianos Kouvaros, Costas Papatheodoropoulos
Hippocampus is importantly involved in dopamine-dependent behaviors and dopamine is a significant modulator of synaptic plasticity in the hippocampus. Moreover, the dopaminergic innervation appears to be disproportionally segregated along the hippocampal longitudinal (dorsoventral) axis with unknown consequences for synaptic plasticity. In this study we examined the actions of endogenously released dopamine and the effects of exogenous D1/D5 dopamine receptor agonists on theta-burst stimulation-induced long-term potentiation (LTP) of field excitatory synaptic potential (fEPSP) at Schaffer collateral-CA1 synapses in slices from dorsal (DH) and ventral hippocampus (VH)...
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
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