Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry

Saura, Josep; Bleuel, Zaiga; Ulrich, J.; Mendelowitsch, Aminadav; Chen, K.; Shih, Jean C.; Malherbe, P.; Prada, M. Da; Richards, John

doi:10.1016/s0306-4522(96)83013-2

Cited by 151 publications

(127 citation statements)

References 54 publications

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“…1989; Saura et al, 1996). Assuming a content of 100 mg proteins per mL tissue, the concentration of MAO-A can be estimated 100 to 300 pmol/mL tissue.…”

Section: Specific Binding Parametersmentioning

confidence: 99%

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Bottlaender

Valette

Delforge

et al. 2009

J Cereb Blood Flow Metab

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[ 11 C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [ 11 C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol-three injections of labeled and/or unlabeled befloxatone-allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B 0 max ) and the apparent in vivo befloxatone affinity (K d ) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n = 5). The cerebellum presented the lowest binding site density (66 ± 13 pmol/mL). Apparent affinity was found to be similar in all structures (K d V R = 6.4±1.5 nmol/L). This study is the first PET-based estimation of the B max of an enzyme.

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“…1989; Saura et al, 1996). Assuming a content of 100 mg proteins per mL tissue, the concentration of MAO-A can be estimated 100 to 300 pmol/mL tissue.…”

Section: Specific Binding Parametersmentioning

confidence: 99%

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Bottlaender

Valette

Delforge

et al. 2009

J Cereb Blood Flow Metab

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“…The oligomers were labelled at the 3' end with terminal deoxynucleotidyl transferase(Life Technologies) and 35S-dATP (New England Nuclear, Boston, MA, U.S.A.) and purified as previously described (Saura et a!., 1996). Cryostat sections of rat brain, adjacent to those used for the binding studies, were mounted on Superfrost Plus slides and then fixed in phosphatebuffered saline (pH 7.4) containing 4% paraformaldehyde for …”

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain

Mutel

Trube

Klingelschmidt

et al. 1998

Journal of Neurochemistry

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The distribution and abundance of specific binding sites (=95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2> binding in layers 3-6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (=2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported. Key Words: a-Amino-3-hydroxy-5-methylisoxazole-4-propionate-9-lmidazol-1 -yl-8-nitro-2,3, 5,6-tetrahydro- High-affinity a-aniino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are ligand-gated cation channels for L-glutalnate, the major excitatory transmitter in the mammalian CNS. Their activation mediates fast transmission at glutamatergic synapses. The receptors, heterooligomeric proteins composed of the subunits G1uR1 -4 with flip and flop forms (Hollmann and Heinemann, 1994;Bettler and Mulle, 1995;Barnard, 1997), play key roles in CNS physiology and pathology. AMPA receptor subunits G1uR1 -4 are differentially regulated during ontogeny, and in adult rat brain they have only partially overlapping distributions (Keinanen et al

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“…MAO-B is found on the outer membrane of the mitochondria, predominately in astrocytes in the brain [23]. The positron emission tomography (PET) radioligand deuterium-L-[ 11 C]deprenyl ([ 11 C]DED) displays high specificity and affinity for MAO-B [24].…”

Section: Introductionmentioning

confidence: 99%

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

et al. 2018

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Purpose: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloidbeta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-L-[ 11 C]deprenyl ([ 11 C]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i.e., two well-established markers of astrogliosis, during Aβ pathology progression. Procedures: APP ArcSwe mice (n = 37) and wild-type (WT) control mice (n = 23), 2-16-month old, were used to investigate biomarkers of astrogliosis. The radioligand, [ 11 C]DED, was used as an in vivo marker while GFAP, vimentin, and MAO-B were used to investigate astrogliosis and macrophage-associated lectin (Mac-2) to investigate microglia/macrophage activation by immunohistochemistry of the mouse brain. Aβ and GFAP levels were also measured with ELISA in brain homogenates. Results: The intrabrain levels of aggregated Aβ and reactive astrocytes were found to be elevated in APP ArcSwe compared with WT mice. GFAP and vimentin expression increased with age, i.e., with Aβ pathology, in the APP ArcSwe mice. This was not the case for in vivo marker [ 11 C]DED that showed elevated binding of the same magnitude in APP ArcSwe mice compared with WT mice at both 8 and 16 months. Further, immunohistochemistry indicated that there was limited co-expression of MAO-B and GFAP. Conclusions: MAO-B levels are increased early in Aβ pathology progression, while GFAP and vimentin appear to increase later, most likely as a consequence of abundant Aβ plaque formation. Thus, [ 11 C]DED is a useful PET radioligand for the detection of changes in MAO-B at an early stage of Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-017-1153-z) contains supplementary material, which is available to authorized users.Correspondence to: Stina Syvänen; e-mail: stina.syvanen@pubcare.uu.se AD progression but does not measure the total extent of astrogliosis at advanced stages of Aβ pathology.

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Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry

Cited by 151 publications

References 54 publications

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

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Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry

Cited by 151 publications

References 54 publications

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [11C]befloxatone and the Multi-Injection Approach

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [11C]befloxatone and the Multi-Injection Approach

Binding Characteristics of a Potent AMPA Receptor Antagonist [3H]Ro 48‐8587 in Rat Brain

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

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In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain