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Michelle W Antoine, Xiaoxia Zhu, Marianne Dieterich, Thomas Brandt, Sarath Vijayakumar, Nicholas McKeehan, Joseph C Arezzo, R Suzanne Zukin, David A Borkholder, Sherri M Jones, Robert D Frisina, Jean M Hébert
How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission...
March 2018: PLoS Biology
Santiago Perez-Lloret, Olivier Rascol
L-DOPA induced dyskinesias (LIDs) may affect up to 40% of Parkinson's disease (PD) and impact negatively health-related quality of life. Amantadine has demonstrated significant antidyskinetic effects in animal PD models and in randomized double-blind placebo-controlled trials (RCTs) in patients with PD. These effects are thought to be related to the blockade of NMDA receptors modulating cortico-striatal glutamatergic-dopaminergic interactions involved in the genesis of LIDs. There are three pharmaceutical forms of amantadine currently available in the market: an oral immediate-release (IR) formulation, which is widely available; an extended-release (ER) formulation (ADS-5102) which has been recently developed and approved by the FDA; and an intravenous infusion (IV) solution, which is not commonly used in clinical practice...
March 7, 2018: Journal of Neural Transmission
Orwa Dandash, Murat Yücel, Rothanthi Daglas, Christos Pantelis, Patrick McGorry, Michael Berk, Alex Fornito
Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months...
March 6, 2018: Translational Psychiatry
Francesca Rizzo, Ester Nespoli, Alireza Abaei, Izhar Bar-Gad, Dinesh K Deelchand, Jörg Fegert, Volker Rasche, Bastian Hengerer, Tobias M Boeckers
Tourette's syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor and vocal tics. Comorbidities such as attention deficit and hyperactivity disorder (ADHD) are observed in over 50% of TS patients. We applied aripiprazole in a juvenile rat model that displays motor tics and hyperactivity. We additionally assessed the amount of ultrasonic vocalizations (USVs) as an indicator for the presence of vocal tics and evaluated the changes in the striatal neurometabolism using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 11...
2018: Frontiers in Neurology
Susanna Waters, Joakim Tedroff, Henrik Ponten, Daniel Klamer, Clas Sonesson, Nicholas Waters
Despite advances in understanding the pathophysiology of Huntington's disease (HD), there are currently no effective pharmacological agents available to treat core symptoms or to stop or prevent the progression of this hereditary neurodegenerative disorder. Pridopidine, a novel small molecule compound, has demonstrated potential for both symptomatic treatment and disease modifying effects in HD. While pridopidine failed to achieve its primary efficacy outcomes (Modified motor score) in two trials (MermaiHD and HART) there were consistent effects on secondary outcomes (TMS)...
2018: Journal of Huntington's Disease
Jun Wu, Daniel Ryskamp, Lutz Birnbaumer, Ilya Bezprozvanny
BACKGROUND: Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice...
2018: Journal of Huntington's Disease
Mieke van Holstein, Monja I Froböse, Jacinta O'Shea, Esther Aarts, Roshan Cools
Motivational, cognitive and action goals are processed by distinct, topographically organized, corticostriatal circuits. We aimed to test whether processing in the striatum is under causal control by cortical regions in the human brain by investigating the effects of offline transcranial magnetic stimulation (TMS) over distinct frontal regions associated with motivational, cognitive and action goal processing. Using a three-session counterbalanced within-subject crossover design, continuous theta burst stimulation was applied over the anterior prefrontal cortex (aPFC), dorsolateral prefrontal cortex, or premotor cortex, immediately after which participants (N = 27) performed a paradigm assessing reward anticipation (motivation), task (cognitive) switching, and response (action) switching...
February 19, 2018: Scientific Reports
Mary C Elliott, Peter M Tanaka, Ryan W Schwark, Rodrigo Andrade
The prefrontal cortex receives a dense serotonergic innervation that plays an important role in its regulation. However, how serotonin regulates different pyramidal and interneuron cell classes in this area is incompletely understood. Previous work in rats has shown that serotonin differentially regulates two classes of pyramidal cells in layer 5. It excites one class by activating 5-HT 2A receptors, whereas it more subtly modulates the integrative properties of the other by co-activating 5-HT 1A and 5-HT 2A receptors...
January 2018: ENeuro
Helena Domin, Łukasz Przykaza, Ewa Kozniewska, Paweł M Boguszewski, Maria Śmiałowska
Our previous studies have shown that ACPT-I [(1S, 3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid], a blood-brain barrier permeable agonist of group III metabotropic glutamate (mGlu) receptors, was neuroprotective against middle cerebral artery occlusion/reperfusion (MCAO/R) in normotensive rats. Preclinical studies are typically performed on healthy animals, whereas stroke patients predominately exhibit comorbidities, such as hypertension; therefore, in the present study, we investigated the effect of ACPT-I in spontaneously hypertensive rats (SHR) after MCAO/R...
February 10, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Janice Jin Hwang, Lisa Parikh, Cheryl Lacadie, Dongju Seo, Wai Lam, Muhammad Hamza, Christian Schmidt, Feng Dai, Anne-Sophie Sejling, Renata Belfort-DeAguiar, R Todd Constable, Rajita Sinha, Robert Sherwin
BACKGROUND: Amongst non-diabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation and executive control. Whether these effects differ in T1DM patients with and without hypoglycemia awareness remains unclear. METHODS: 42 individuals (13 healthy control subjects (HC), 16 T1DM individuals with hypoglycemia awareness (T1DM-Aware) and 13 T1DM individuals with hypoglycemia unawareness (T1DM-Unaware)) underwent BOLD fMRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia...
January 30, 2018: Journal of Clinical Investigation
Anna S Huang, Jameson A Mitchell, Suzanne N Haber, Nelly Alia-Klein, Rita Z Goldstein
Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Henriette Edemann-Callesen, Bettina Habelt, Franziska Wieske, Mark Jackson, Niranjan Khadka, Daniele Mattei, Nadine Bernhardt, Andreas Heinz, David Liebetanz, Marom Bikson, Frank Padberg, Ravit Hadar, Michael A Nitsche, Christine Winter
Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS...
January 10, 2018: Translational Psychiatry
Genevra Hart, Laura A Bradfield, Bernard W Balleine
The acquisition of goal-directed action requires encoding the association between an action and its specific consequences or outcome. At a neural level, this encoding has been hypothesized to involve a prefrontal corticostriatal circuit involving the projection from the prelimbic cortex (PL) to the posterior dorsomedial striatum (pDMS); however, no direct evidence for this claim has been reported. In a series of experiments, we performed functional disconnection of this pathway using targeted lesions of the anterior corpus callosum to disrupt contralateral corticostriatal projections with asymmetrical lesions of the PL and/or pDMS to block plasticity in this circuit in rats...
January 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Masahiko Tomiyama
Symptomatic characteristics and recent advances in understanding the pathophysiology of tardive dyskinesias and levodopa-induced dyskinesias were reviewed. After the advent of atypical antipsychotics, tardive dyskinesias became less frequent, at least as observed during a short-term follow up. The dopamine supersensitivity hypothesis stating that blockade of dopamine D2 receptors by antipsychotics makes D2 receptors more sensitive to dopamine, has long been proposed. However, the true mechanisms remain to be determined...
December 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
Ricardo Márquez-Gómez, Meridith T Robins, Citlaly Gutiérrez-Rodelo, Juan-Manuel Arias, Jesús-Alberto Olivares-Reyes, Richard M van Rijn, José-Antonio Arias-Montaño
In the striatum, histamine H3 receptors (H3 Rs) are co-expressed with adenosine A2A receptors (A2A Rs) in the cortico-striatal glutamatergic afferents and the GABAergic medium-sized spiny neurons that originate the indirect pathway of the basal ganglia. This location allows H3 Rs and A2A Rs to regulate the striatal GABAergic and glutamatergic transmission. However, whether these receptors can physically interact has not yet been assessed. To test this hypothesis, a heteromer-selective in vitro assay was used to detect functional complementation between a chimeric A2A R302 -Gαqi4 and wild-type H3 Rs in transfected HEK-293T cells...
March 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Matthew B Veldman, X William Yang
Huntington's disease (HD), a dominantly inherited neurodegenerative disease, is defined by its genetic cause, a CAG-repeat expansion in the HTT gene, its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons (MSNs). However, the molecular mechanisms from genetic lesion to disease phenotype remain largely unclear. Mouse models of HD have been created that exhibit phenotypes partially recapitulating those in the patient, and specifically, cortico-striatal disconnectivity appears to be a shared pathogenic event shared by HD mouse models and patients...
November 7, 2017: Current Opinion in Neurobiology
Giada Spigolon, Anna Cavaccini, Massimo Trusel, Raffaella Tonini, Gilberto Fisone
The cJun N-terminal kinase (JNK) signaling pathway has been extensively studied with regard to its involvement in neurodegenerative processes, but little is known about its functions in neurotransmission. In a mouse model of Parkinson's disease (PD), we show that the pharmacological activation of dopamine D1 receptors (D1R) produces a large increase in JNK phosphorylation. This effect is secondary to dopamine depletion, and is restricted to the striatal projection neurons that innervate directly the output structures of the basal ganglia (dSPN)...
February 2018: Neurobiology of Disease
Yiquan Shi, Uta Wolfensteller, Torsten Schubert, Hannes Ruge
Cognitive flexibility is essential to cope with changing task demands and often it is necessary to adapt to combined changes in a coordinated manner. The present fMRI study examined how the brain implements such multi-level adaptation processes. Specifically, on a "local," hierarchically lower level, switching between two tasks was required across trials while the rules of each task remained unchanged for blocks of trials. On a "global" level regarding blocks of twelve trials, the task rules could reverse or remain the same...
November 2, 2017: Human Brain Mapping
Ni Ni Soe, Daniel J Wen, Joann S Poh, Yap-Seng Chong, Birit Fp Broekman, Helen Chen, Lynette P Shek, Kok Hian Tan, Peter D Gluckman, Marielle V Fortier, Michael J Meaney, Anqi Qiu
Perinatal maternal depressive symptoms influence brain development of offspring. Such effects are particularly notable in the amygdala, a key structure involved in emotional processes. This study investigated whether the functional organization of the amygdala varies as a function of pre- and postnatal maternal depressive symptoms. The amygdala functional network was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) in 128 children at age of 4.4 to 4.8 years. Maternal depressive symptoms were obtained at 26 weeks of gestation, 3 months, 1, 2, 3, and 4...
November 2, 2017: Human Brain Mapping
Rageen Rajendram, Sefi Kronenberg, Christie L Burton, Paul D Arnold
OBJECTIVE: Obsessive-compulsive disorder (OCD) is common and debilitating with patients exhibiting persistent intrusive thoughts (obsessions), repetitive ritualistic behaviours (compulsions) and anxiety. While it is known that OCD is highly heritable, the specific genetic risk factors for OCD are still largely unknown. The etiology of OCD has also not been fully elucidated but there is growing evidence that glutamate signaling dysfunction in the cortico-striatal-thalamo-cortical (CSTC) circuitry plays a role in its pathogenesis...
2017: Journal of the Canadian Academy of Child and Adolescent Psychiatry
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