Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain
We have investigated to what extent microinjected β-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at d...
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| Veröffentlicht in: | Brain research 2005-04, Vol.1041 (2), p.167-180 |
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| creator | Höistad, Malin Samskog, Jenny Jacobsen, Kirsten X. Olsson, Annika Hansson, Hans-Arne Brodin, Ernst Fuxe, Kjell |
| description | We have investigated to what extent microinjected β-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for β-endorphin and μ-opioid receptors. The β-endorphin injected rats showed a marked increase in β-endorphin immunoreactive (IR) material in the CSF, with a peak at 30–45 min post-injection, and this β-endorphin-IR material existed mainly as the intact β-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct β-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous β-endorphin. The β-endorphin-IR in several of the globus pallidus cell bodies colocalized with the μ-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic β-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain. |
| doi_str_mv | 10.1016/j.brainres.2005.02.014 |
| format | Article |
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Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for β-endorphin and μ-opioid receptors. The β-endorphin injected rats showed a marked increase in β-endorphin immunoreactive (IR) material in the CSF, with a peak at 30–45 min post-injection, and this β-endorphin-IR material existed mainly as the intact β-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct β-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous β-endorphin. The β-endorphin-IR in several of the globus pallidus cell bodies colocalized with the μ-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic β-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2005.02.014</identifier><identifier>PMID: 15829226</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Animals ; arcuate nucleus ; beta-Endorphin - administration & dosage ; beta-Endorphin - cerebrospinal fluid ; beta-Endorphin - pharmacokinetics ; Biological and medical sciences ; central-nervous-system ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Cerebrospinal Fluid - chemistry ; Cerebrospinal Fluid - physiology ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Diffusion ; electrical-stimulation ; Extracellular Space - drug effects ; Extracellular Space - metabolism ; Fundamental and applied biological sciences. Psychology ; Globus Pallidus - cytology ; Globus Pallidus - drug effects ; Globus Pallidus - metabolism ; growth-factor ; Immunohistochemistry ; Intraparenchymal injections ; Lateral Ventricles - physiology ; Male ; Mass Spectrometry ; mediated endocytosis ; Microinjections ; Migration ; mu-opioid receptor ; Neurons - drug effects ; Neurons - metabolism ; Neurosciences ; Neurovetenskaper ; periaqueductal gray ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu - drug effects ; Receptors, Opioid, mu - metabolism ; Septal Nuclei - cytology ; Septal Nuclei - drug effects ; Septal Nuclei - metabolism ; spinal-cord ; Time Factors ; ventriculocisternal perfusate ; Vertebrates: nervous system and sense organs ; Volume transmission</subject><ispartof>Brain research, 2005-04, Vol.1041 (2), p.167-180</ispartof><rights>2005 Elsevier B.V.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-471d98a65c45cc1ef6a6ce5e75f8bca2a68408e18203daedeedfce8774182a3d3</citedby><cites>FETCH-LOGICAL-c533t-471d98a65c45cc1ef6a6ce5e75f8bca2a68408e18203daedeedfce8774182a3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899305002313$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16713773$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15829226$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/81744$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1956230$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Höistad, Malin</creatorcontrib><creatorcontrib>Samskog, Jenny</creatorcontrib><creatorcontrib>Jacobsen, Kirsten X.</creatorcontrib><creatorcontrib>Olsson, Annika</creatorcontrib><creatorcontrib>Hansson, Hans-Arne</creatorcontrib><creatorcontrib>Brodin, Ernst</creatorcontrib><creatorcontrib>Fuxe, Kjell</creatorcontrib><title>Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>We have investigated to what extent microinjected β-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for β-endorphin and μ-opioid receptors. The β-endorphin injected rats showed a marked increase in β-endorphin immunoreactive (IR) material in the CSF, with a peak at 30–45 min post-injection, and this β-endorphin-IR material existed mainly as the intact β-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct β-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous β-endorphin. The β-endorphin-IR in several of the globus pallidus cell bodies colocalized with the μ-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic β-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.</description><subject>Animals</subject><subject>arcuate nucleus</subject><subject>beta-Endorphin - administration & dosage</subject><subject>beta-Endorphin - cerebrospinal fluid</subject><subject>beta-Endorphin - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>central-nervous-system</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Cerebrospinal Fluid - chemistry</subject><subject>Cerebrospinal Fluid - physiology</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Diffusion</subject><subject>electrical-stimulation</subject><subject>Extracellular Space - drug effects</subject><subject>Extracellular Space - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Globus Pallidus - cytology</subject><subject>Globus Pallidus - drug effects</subject><subject>Globus Pallidus - metabolism</subject><subject>growth-factor</subject><subject>Immunohistochemistry</subject><subject>Intraparenchymal injections</subject><subject>Lateral Ventricles - physiology</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>mediated endocytosis</subject><subject>Microinjections</subject><subject>Migration</subject><subject>mu-opioid receptor</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurosciences</subject><subject>Neurovetenskaper</subject><subject>periaqueductal gray</subject><subject>Radioimmunoassay</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Opioid, mu - drug effects</subject><subject>Receptors, Opioid, mu - metabolism</subject><subject>Septal Nuclei - cytology</subject><subject>Septal Nuclei - drug effects</subject><subject>Septal Nuclei - metabolism</subject><subject>spinal-cord</subject><subject>Time Factors</subject><subject>ventriculocisternal perfusate</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Volume transmission</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAQxy0EokvhFapc4ESCv-3cQOVTqsQFzpZjT1qHbBzspIjX4kF4JrzdQE9oJUv2zPxmPPb8EboguCGYyFdD0yUbpgS5oRiLBtMGE_4A7YhWtJaU44dohzGWtW5bdoae5DwUk7EWP0ZnRGjaUip3aHgLC7glxKmKffX7Vw2Tj2m-CVNV1nIDlYMEXYp5DpMdq35cg69sv0AqwJJsXlKwS4nsg0sxTMNWrQTjXX6yS3XX61P0qLdjhmfbfo6-vn_35fJjffX5w6fLN1e1E4wtNVfEt9pK4bhwjkAvrXQgQIled85SKzXHGoimmHkLHsD3DrRSvLgs8-wc1ce6-QfMa2fmFPY2_TTRBrO5vpUTGKEJVbrwL__LX6-zKa7r9cBrojgv-IsjPqf4fYW8mH3IDsbRThDXbKRSTEvNToIUK0KZEidBohgXmB9AeQTLT-ecoP_XK8HmIAszmL-yMAdZGExNkUVJvNhuWLs9-Pu0TQcFeL4BNjs79slOLuR7TirCyrsK9_rIQRngbYBksgswOfAhlcEbH8OpXv4AWobddQ</recordid><startdate>20050418</startdate><enddate>20050418</enddate><creator>Höistad, Malin</creator><creator>Samskog, Jenny</creator><creator>Jacobsen, Kirsten X.</creator><creator>Olsson, Annika</creator><creator>Hansson, Hans-Arne</creator><creator>Brodin, Ernst</creator><creator>Fuxe, Kjell</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope></search><sort><creationdate>20050418</creationdate><title>Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain</title><author>Höistad, Malin ; Samskog, Jenny ; Jacobsen, Kirsten X. ; Olsson, Annika ; Hansson, Hans-Arne ; Brodin, Ernst ; Fuxe, Kjell</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-471d98a65c45cc1ef6a6ce5e75f8bca2a68408e18203daedeedfce8774182a3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>arcuate nucleus</topic><topic>beta-Endorphin - administration & dosage</topic><topic>beta-Endorphin - cerebrospinal fluid</topic><topic>beta-Endorphin - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>central-nervous-system</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Cerebrospinal Fluid - chemistry</topic><topic>Cerebrospinal Fluid - physiology</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Diffusion</topic><topic>electrical-stimulation</topic><topic>Extracellular Space - drug effects</topic><topic>Extracellular Space - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Globus Pallidus - cytology</topic><topic>Globus Pallidus - drug effects</topic><topic>Globus Pallidus - metabolism</topic><topic>growth-factor</topic><topic>Immunohistochemistry</topic><topic>Intraparenchymal injections</topic><topic>Lateral Ventricles - physiology</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>mediated endocytosis</topic><topic>Microinjections</topic><topic>Migration</topic><topic>mu-opioid receptor</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurosciences</topic><topic>Neurovetenskaper</topic><topic>periaqueductal gray</topic><topic>Radioimmunoassay</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Opioid, mu - drug effects</topic><topic>Receptors, Opioid, mu - metabolism</topic><topic>Septal Nuclei - cytology</topic><topic>Septal Nuclei - drug effects</topic><topic>Septal Nuclei - metabolism</topic><topic>spinal-cord</topic><topic>Time Factors</topic><topic>ventriculocisternal perfusate</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Volume transmission</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Höistad, Malin</creatorcontrib><creatorcontrib>Samskog, Jenny</creatorcontrib><creatorcontrib>Jacobsen, Kirsten X.</creatorcontrib><creatorcontrib>Olsson, Annika</creatorcontrib><creatorcontrib>Hansson, Hans-Arne</creatorcontrib><creatorcontrib>Brodin, Ernst</creatorcontrib><creatorcontrib>Fuxe, Kjell</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Höistad, Malin</au><au>Samskog, Jenny</au><au>Jacobsen, Kirsten X.</au><au>Olsson, Annika</au><au>Hansson, Hans-Arne</au><au>Brodin, Ernst</au><au>Fuxe, Kjell</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2005-04-18</date><risdate>2005</risdate><volume>1041</volume><issue>2</issue><spage>167</spage><epage>180</epage><pages>167-180</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>We have investigated to what extent microinjected β-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for β-endorphin and μ-opioid receptors. The β-endorphin injected rats showed a marked increase in β-endorphin immunoreactive (IR) material in the CSF, with a peak at 30–45 min post-injection, and this β-endorphin-IR material existed mainly as the intact β-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct β-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous β-endorphin. The β-endorphin-IR in several of the globus pallidus cell bodies colocalized with the μ-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic β-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>15829226</pmid><doi>10.1016/j.brainres.2005.02.014</doi><tpages>14</tpages></addata></record> |
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| ispartof | Brain research, 2005-04, Vol.1041 (2), p.167-180 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals arcuate nucleus beta-Endorphin - administration & dosage beta-Endorphin - cerebrospinal fluid beta-Endorphin - pharmacokinetics Biological and medical sciences central-nervous-system Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebrospinal Fluid - chemistry Cerebrospinal Fluid - physiology Corpus Striatum - drug effects Corpus Striatum - metabolism Diffusion electrical-stimulation Extracellular Space - drug effects Extracellular Space - metabolism Fundamental and applied biological sciences. Psychology Globus Pallidus - cytology Globus Pallidus - drug effects Globus Pallidus - metabolism growth-factor Immunohistochemistry Intraparenchymal injections Lateral Ventricles - physiology Male Mass Spectrometry mediated endocytosis Microinjections Migration mu-opioid receptor Neurons - drug effects Neurons - metabolism Neurosciences Neurovetenskaper periaqueductal gray Radioimmunoassay Rats Rats, Sprague-Dawley Receptors, Opioid, mu - drug effects Receptors, Opioid, mu - metabolism Septal Nuclei - cytology Septal Nuclei - drug effects Septal Nuclei - metabolism spinal-cord Time Factors ventriculocisternal perfusate Vertebrates: nervous system and sense organs Volume transmission |
| title | Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain |
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