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Low affinity α1/α2 containing GABAA receptors are significantly less able to bind [11C]/[3H]Ro15‐4513 following translocation to the endosomal environment. The alterations in [11C]Ro15‐4513 binding observed in vivo following perturbations in endogenous GABA are likely driven by both alterations in receptor binding parameters following agonist induced internalisation and the GABA Shift.
The rat globus pallidus (GP) is homologous to the primate GP externus. Studies with injectable anesthetics suggest that GP neurons can be classified into Type‐I and Type‐II cells based on extracellularly recorded spike shape, or positively coupled (PC), negatively coupled (NC), and uncoupled (UC) cells based on functional connectivity with the cortex. In this study, we examined the electrophysiology...
Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [13N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate‐glutamine pathway. The present study investigated the effect of an inhibitor of GS on [13N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the...
Using whole‐brain structural measures coupled to analysis of salivary brain‐derived neurotrophic factor (BDNF), we demonstrate sensory motor training‐induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level.
Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with...
Decreased glutamatergic neurotransmission is hypothesized to be involved in the pathophysiology of schizophrenia. Inhibition of glycine transporter Type‐1 (GlyT1) reuptake is expected to increase the glutamatergic neurotransmission and may serve as treatment for cognitive and negative symptoms of schizophrenia. In this article, we present human data from a novel GlyT1 PET tracer, [18F]MK‐6577. In...
The authors demonstrate that different NMDAR antagonists (ketamine and MK‐801) have varying effects on spine density depending on dose, drug regimen, and brain region. While acute ketamine treatment increases cortical spine density in mice, subchronic exposure to either drug reduces spine density in both the cortex and striatum.
The efficient radiosynthesis for the MAO‐A ligand [18F]fluoroethyl‐harmol is reported. Initial PET examinations reveal the ligand to be retained throughout rat brain during 90 min, whereas pretreatment with pargyline results in substantially increased washout, from which binding potentials in the range of 1.4–2.1 can be calculated.
Sleep is a fundamental state necessary for maintenance of physical and neurological homeostasis throughout life. Several studies regarding the functions of sleep have been focused on effects of sleep deprivation on synaptic plasticity at a molecular and electrophysiological level, and only a few studies have studied sleep function from a structural perspective. Moreover, during normal aging, sleep...
We report the use of β3 adrenergic receptor mediated activation of rat brain frontal cortex using mirabegron (a selective β3 adrenoceptor agonist), measured by 18F‐FDG PET/CT. Another β3 agonist, CL 316,243, did not have this effect due to impermeability through the blood brain barrier (BBB), while atomoxetine, a norepinephrine transporter blocker, did increase 18F‐FDG uptake in the frontal cortex...
[11C]MP‐10 is a potent and specific PET tracer previously shown to be suitable for imaging the phosphodiesterase 10A (PDE10A) in baboons with reversible kinetics and high specific binding. However, another report indicated that [11C]MP‐10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood‐brain‐barrier...
The serotonin 5‐HT2C receptor has shown promise in vivo as a pharmacotherapeutic target for alcoholism. For example, recently, a novel 4‐phenyl‐2‐N,N‐dimethylaminotetralin (PAT) drug candidate, that demonstrates 5‐HT2C receptor agonist activity together with 5‐HT2A/2B receptor inverse agonist activity, was shown to reduce operant responding for ethanol after peripheral administration to rats. Previous...
Dynamin 1 is a neuron‐specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium–pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures...
Renin–angiotensin system overactivity, upregulation of postsynaptic NMDA receptor function, and increased reactive oxygen species (ROS) production in the hypothalamic paraventricular nucleus (PVN) are hallmarks of angiotensin II (AngII)‐induced hypertension, which is far more common in young males than in young females. We hypothesize that the sex differences in hypertension are related to differential...
Mitochondrial dysfunctions have been implicated in the progression of Huntington's disease (HD). To date, several free radical scavengers have been tested in experimental HD, but only a few have shown promise. Although most antioxidants rapidly reduce ROS but in the process they are oxidized, which limits their ability to protect. Therefore, in the present study we employed a potent recycling antioxidant,...
The specific mechanisms by which serotonin (5‐HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole‐cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5‐HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found...
This study explored the use of the α2C‐adrenoceptor PET tracer [11C]ORM‐13070 to monitor α2C‐AR occupancy in the human brain. The subtype‐nonselective α2‐AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency (Emax and EC50) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations...
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