Neonatal domoic acid alters in vivo binding of [11C]yohimbine to α2-adrenoceptors in adult rat brain

Thomsen, Majken Borup; Lillethorup, Thea Pinholt; Jakobsen, Steen; Nielsen, Erik H.; Simonsen, Mette Kildevæld; Wegener, Gregers; Landau, Anne M.; Tasker, R. Andrew

doi:10.1007/s00213-016-4416-5

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…To determine the occupancy by LEV at different doses, a Lassen occupancy plot was applied across all the defined VOIs. The plasma-free fraction (ƒ P ) was determined as described earlier 17 using plasma from four rats. We also calculated k3/k4 as an estimate of binding potential; however, due to the high standard error associated with this estimation and the large variability (up to 100%) across animals, we do not present these data.…”

Section: Methodsmentioning

confidence: 99%

In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET

Thomsen

Jacobsen

Lillethorup

et al. 2020

J Cereb Blood Flow Metab

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The number of functionally active synapses provides a measure of neural integrity, with reductions observed in neurodegenerative disorders. [11C]UCB-J binds to synaptic vesicle 2A (SV2A) transmembrane protein located in secretory vesicles. We aimed to assess [11C]UCB-J PET as an in vivo biomarker of regional cerebral synaptic SV2A density in rat lesion models of neurodegeneration. Healthy anesthetized rats had [11C]UCB-J PET and arterial blood sampling. We compared different models describing [11C]UCB-J brain uptake kinetics to determine its regional distribution. Blocking studies were performed with levetiracetam (LEV), an antiepileptic SV2A antagonist. Tracer binding was measured in rodent unilateral acute lesion models of Parkinsonism and Huntington’s disease, induced with 6-hydroxydopamine (6-OHDA) and quinolinic acid (QA), respectively. [3H]UCB-J autoradiography was performed in postmortem tissue. Rat brain showed high and fast [11C]UCB-J uptake and washout with up to 80% blockade by LEV. [11C]UCB-J PET showed a 6.2% decrease in ipsilateral striatal SV2A binding after 6-OHDA and 39.3% and 55.1% decreases after moderate and high dose QA confirmed by autoradiography. In conclusion, [11C]UCB-J PET provides a good in vivo marker of synaptic SV2A density which can potentially be followed longitudinally along with synaptic responses to putative neuroprotective agents in models of neurodegeneration.

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Section: Methodsmentioning

confidence: 99%

In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET

Thomsen

Jacobsen

Lillethorup

et al. 2020

J Cereb Blood Flow Metab

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“…The labeling of yohimbine with carbon-11 provided new opportunities to measure noradrenergic transmission in pathological conditions. [ 11 C]yohimbine so far has been applied to image α 2 adrenoceptor in vivo in different species, including humans 12 , pigs 13 , 14 , and rats 15 – 17 . However, the wide anatomical distribution of noradrenergic receptors complicates the quantification of receptor occupancy and receptor density.…”

Section: Introductionmentioning

confidence: 99%

Radioligand binding analysis of α2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

Phan

Landau

Jakobsen

et al. 2017

Sci Rep

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We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [11C]yohimbine binding in brain to quantify the density and affinity of α2 adrenoceptors under condition of changing radioligand binding to plasma proteins. We obtained dynamic PET recordings from brain of Spraque Dawley rats at baseline, followed by pharmacological challenge with unlabeled yohimbine (0.3 mg/kg). The challenge with unlabeled ligand failed to diminish radioligand accumulation in brain tissue, due to the blocking of radioligand binding to plasma proteins that elevated the free fractions of the radioligand in plasma. We devised a method that graphically resolved the masking of unlabeled ligand binding by the increase of radioligand free fractions in plasma. The Extended Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50–60% in the presence of unlabeled ligand. The kinetic unmasking of inhibited binding reflected in the increase of the reference volume of distribution yielded estimates of receptor saturation consistent with the binding of unlabeled ligand.

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“…It has been widely used as AMPA/kainate receptor agonist in neurotoxicity studies in learning and memory disease models [6,56,57] . Recent study indicate that DA induces long-term changes in α2-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype [58] .…”

Section: Marine Neurotoxins Interacting With Other Receptorsmentioning

confidence: 99%

Marine Neurotoxins: a Double-edged Sword in Food Industry and Brain Research

Huang¹,

Gong²,

Xue³

et al. 2017

Med One

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Marine organisms are important food resource for human. Diversified neurotoxins have been found in marine organisms. In order to effect effectively in ocean, marine neurotoxins are often multiplied potent than other toxins. Therefore the safety of marine products is critical for human health. Here we summarize the current potent marine neurotoxins and their derivatives based on their latest application in neuron science research. Their toxicity mechanism is also discussed. Most of the toxins specifically act on ion channels including Na + , K + , Ca 2+ channels, a few interact with receptors like glutamate receptor or nicotinic acetylcholine receptors thus can have effect on neurons. They are frequently used as agonist or antagonist either blockade the channel or excite the potential. Overall, it is worthwhile to make use of this double-edged sword pharmacologically and scientifically.

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Neonatal domoic acid alters in vivo binding of [11C]yohimbine to α2-adrenoceptors in adult rat brain

Abstract: The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long-term changes in α-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype.

Cited by 6 publications

References 31 publications

In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET

In vivo imaging of synaptic SV2A protein density in healthy and striatal-lesioned rats with [11C]UCB-J PET

Radioligand binding analysis of α2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

Marine Neurotoxins: a Double-edged Sword in Food Industry and Brain Research

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