Commit 70223cfc authored by Vesa Oikonen's avatar Vesa Oikonen
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title: Analysis of [C-11]PBR28 title: Analysis of [C-11]PBR28
author: Vesa Oikonen, Jouni Tuisku author: Vesa Oikonen, Jouni Tuisku
updated_at: 2021-04-23 updated_at: 2021-04-27
created_at: 2015-08-03 created_at: 2015-08-03
tags: tags:
- Inflammation - Inflammation
...@@ -18,7 +18,8 @@ tags: ...@@ -18,7 +18,8 @@ tags:
<p>PBR28 is a selective second-generation ligand with high affinity for the <p>PBR28 is a selective second-generation ligand with high affinity for the
<a href="./target_tspo.html">translocator protein (TSPO)</a>, formerly known as peripheral <a href="./target_tspo.html">translocator protein (TSPO)</a>, formerly known as peripheral
benzodiazepine receptor (PBR), a marker of <a href="./target_inflammation.html">inflammation</a>. benzodiazepine receptor (PBR), a marker of <a href="./mitochondria.html#TSPO">mitochondria</a> and
<a href="./target_inflammation.html">inflammation</a>.
Increased distribution volume of [<sup>11</sup>C]PBR28 has been observed in Increased distribution volume of [<sup>11</sup>C]PBR28 has been observed in
<a href="./organ_brain.html">the brain</a> of baboons and humans after injection of <em>E. Coli</em> <a href="./organ_brain.html">the brain</a> of baboons and humans after injection of <em>E. Coli</em>
lipopolysaccharide lipopolysaccharide
...@@ -26,7 +27,7 @@ lipopolysaccharide ...@@ -26,7 +27,7 @@ lipopolysaccharide
<a href="https://doi.org/10.1073/pnas.1511003112">Sandiego et al, 2015</a>; <a href="https://doi.org/10.1073/pnas.1511003112">Sandiego et al, 2015</a>;
<a href="https://doi.org/10.1016/j.nucmedbio.2014.11.003">Yoder et al, 2015</a>). <a href="https://doi.org/10.1016/j.nucmedbio.2014.11.003">Yoder et al, 2015</a>).
The cerebral artery occlusion model of neuroinflammation and <a href="./dis_stroke.html">stroke</a> The cerebral artery occlusion model of neuroinflammation and <a href="./dis_stroke.html">stroke</a>
in rats has shown a localized increase in [<sup>11</sup>C]PBR28 SUV in rats has shown a localized increase in [<sup>11</sup>C]PBR28 <a href="./model_suv.html">SUV</a>
(<a href="https://doi.org/10.1016/j.neulet.2006.09.093">Imaizumi et al, 2007</a>; (<a href="https://doi.org/10.1016/j.neulet.2006.09.093">Imaizumi et al, 2007</a>;
<a href="https://doi.org/10.1007/s00429-014-0970-y">T&oacute;th et al, 2016</a>), <a href="https://doi.org/10.1007/s00429-014-0970-y">T&oacute;th et al, 2016</a>),
and that increase could be reversed by injection of PK11195 and that increase could be reversed by injection of PK11195
...@@ -242,8 +243,8 @@ cerebellum as pseudo-reference region. ...@@ -242,8 +243,8 @@ cerebellum as pseudo-reference region.
<a href="https://doi.org/10.1186/s13550-016-0226-3">Nair et al (2016)</a> reported that the best <a href="https://doi.org/10.1186/s13550-016-0226-3">Nair et al (2016)</a> reported that the best
test-retest variability in AD study was obtained when using whole brain as the pseudo-reference. test-retest variability in AD study was obtained when using whole brain as the pseudo-reference.
Whole brain has been used as reference to calculate SUVR maps from data range 60-90 min in several Whole brain (not including the ventricles) has been used as reference to calculate SUVR maps from
brain studies data range 60-90 min in several brain studies
(<a href="https://doi.org/10.1093/brain/awu377">Loggia et al., 2015</a>; (<a href="https://doi.org/10.1093/brain/awu377">Loggia et al., 2015</a>;
<a href="https://doi.org/10.1016/j.nicl.2015.01.009">Zürcher et al., 2015</a>; <a href="https://doi.org/10.1016/j.nicl.2015.01.009">Zürcher et al., 2015</a>;
<a href="https://doi.org/10.1038/s41380-019-0433-1">Albrecht et al., 2021</a>). <a href="https://doi.org/10.1038/s41380-019-0433-1">Albrecht et al., 2021</a>).
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title: Mitochondria title: Mitochondria
author: Vesa Oikonen author: Vesa Oikonen
updated_at: 2021-03-26 updated_at: 2021-04-27
created_at: 2017-09-20 created_at: 2017-09-20
tags: tags:
- Mitochondria - Mitochondria
...@@ -226,7 +226,11 @@ tissues, and low levels in <a href="./organ_brain.html">the brain</a> and ...@@ -226,7 +226,11 @@ tissues, and low levels in <a href="./organ_brain.html">the brain</a> and
<a href="./organ_liver.html">liver</a>. In the brain parenchyma TSPO is located in glial cells, and <a href="./organ_liver.html">liver</a>. In the brain parenchyma TSPO is located in glial cells, and
has thus been used as a biomarker of activated glial cells. It can also be found in other has thus been used as a biomarker of activated glial cells. It can also be found in other
inflammatory cells. Generally, <a href="./target_tspo.html">TSPO</a> imaging might have potential in inflammatory cells. Generally, <a href="./target_tspo.html">TSPO</a> imaging might have potential in
studying the concentration of viable mitochondria in tissues.</p> studying the concentration of viable mitochondria in tissues.
For instance, regional uptake of TSPO radioligand
<a href="./analysis_11c-pbr28.html">[<sup>11</sup>C]PBR28</a> was lower in subjects with autism
spectrum disorder in brain regions associated with sociocognitive processes
(<a href="https://doi.org/10.1038/s41380-020-0682-z">Zürcher et al., 2020</a>).</p>
<h3>P2X<sub>7</sub>R</h3> <h3>P2X<sub>7</sub>R</h3>
......
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title: TSPO title: TSPO
author: Vesa Oikonen author: Vesa Oikonen
updated_at: 2021-04-19 updated_at: 2021-04-27
created_at: 2012-09-14 created_at: 2012-09-14
tags: tags:
- TSPO - TSPO
...@@ -14,19 +14,29 @@ tags: ...@@ -14,19 +14,29 @@ tags:
<p>The translocator protein 18kDa (TSPO), earlier called peripheral benzodiazepine receptor (PBR) <p>The translocator protein 18kDa (TSPO), earlier called peripheral benzodiazepine receptor (PBR)
and mitochondrial benzodiazepine receptor, is a five transmembrane domain protein that is localized and mitochondrial benzodiazepine receptor, is a five transmembrane domain protein.
mainly in steroid-synthesizing tissues. Secretory and glandular tissues, such as TSPO is mainly situated in the outer <a href="./mitochondria.html">mitochondrial</a> membrane,
<a href="./organ_adrenal_gland.html">adrenal glands</a>, pineal gland, salivary glands, and but it is also present in Golgi apparatus, lysosomes, peroxisomes, nucleus, and on plasma membrane,
olfactory epithelium contain high levels of TSPO; intermediate levels in renal and myocardial also in mature <a href="./rbc.html">human red cells</a>
tissues, and low levels in <a href="./organ_brain.html">the brain</a> and (<a href="https://doi.org/10.1016/j.mce.2010.06.013">Batarseh &amp; Papadopoulos, 2010</a>).
<a href="./organ_liver.html">liver</a> In mitochondria, TSPO may have role in transporting cholesterol into mitochondria,
and TSPO concentrations are high in steroid producing tissues.
TSPO ligands modulate mitochondrial and cytosolic Ca<sup>2+</sup> dynamics.</p>
<p>Secretory and glandular tissues, such as <a href="./organ_adrenal_gland.html">adrenal glands</a>,
pineal gland, salivary glands, and olfactory epithelium contain high levels of TSPO;
intermediate levels in <a href="./organ_kidney.html">renal</a> and
<a href="./organ_heart.html">myocardial</a> tissues, and
low levels in <a href="./organ_brain.html">the brain</a> and <a href="./organ_liver.html">liver</a>
(<a href="http://www.ncbi.nlm.nih.gov/pubmed/10581326">Gavish et al., 1999</a>; (<a href="http://www.ncbi.nlm.nih.gov/pubmed/10581326">Gavish et al., 1999</a>;
<a href="https://doi.org/10.1016/j.mce.2010.06.013">Batarseh &amp; Papadopoulos, 2010</a>). <a href="https://doi.org/10.1016/j.mce.2010.06.013">Batarseh &amp; Papadopoulos, 2010</a>).
In the brain parenchyma TSPO is located in glial cells, and has thus been used In the brain parenchyma TSPO is located in glial cells (microglia and astrocytes), and has thus been
as a biomarker of activated glial cells used as a biomarker of activated glial cells
(<a href="https://doi.org/10.1016/j.pharmthera.2007.12.004">Chen &amp; Guilarte, 2008</a>; (<a href="https://doi.org/10.1016/j.pharmthera.2007.12.004">Chen &amp; Guilarte, 2008</a>;
<a href="https://doi.org/10.1007/s13139-017-0475-8">Alam et al., 2017</a>; <a href="https://doi.org/10.1007/s13139-017-0475-8">Alam et al., 2017</a>;
<a href="https://doi.org/10.1007/s12149-020-01530-2">Nomura et al., 2021</a>). <a href="https://doi.org/10.1007/s12149-020-01530-2">Nomura et al., 2021</a>).
Mitochondrial dysfunction or abnormal microglia autophagy may be seen as reduced TSPO expression
(<a href="https://doi.org/10.1038/s41380-020-0682-z">Zürcher et al., 2020</a>).
Outside of the brain, TSPO is expressed in macrophages, and could be targeted in Outside of the brain, TSPO is expressed in macrophages, and could be targeted in
<a href="./target_inflammation.html">inflammation imaging</a>.</p> <a href="./target_inflammation.html">inflammation imaging</a>.</p>
...@@ -37,13 +47,6 @@ differentiation, and <a href="./ros.html">oxidative stress</a>, depending on the ...@@ -37,13 +47,6 @@ differentiation, and <a href="./ros.html">oxidative stress</a>, depending on the
TSPO has been found to be upregulated in certain <a href="./tumour.html#inflammation">tumours</a>. TSPO has been found to be upregulated in certain <a href="./tumour.html#inflammation">tumours</a>.
</p> </p>
<p>TSPO is mainly situated in the outer <a href="./mitochondria.html">mitochondrial</a> membrane,
but it is also present in Golgi apparatus, lysosomes, peroxisomes, nucleus, and on plasma membrane,
also in mature <a href="./rbc.html">human red cells</a>
(<a href="https://doi.org/10.1016/j.mce.2010.06.013">Batarseh &amp; Papadopoulos, 2010</a>).
In mitochondria, TSPO may have role in transporting cholesterol into mitochondria,
and TSPO concentrations are high in steroid producing tissues.
TSPO ligands modulate mitochondrial and cytosolic Ca<sup>2+</sup> dynamics.</p>
<p>In humans, <a name="rs6971">rs6971 polymorphism</a> in the TSPO gene affects the binding of <p>In humans, <a name="rs6971">rs6971 polymorphism</a> in the TSPO gene affects the binding of
many TSPO ligands, and cholesterol. many TSPO ligands, and cholesterol.
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