Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons
Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (
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| Veröffentlicht in: | Journal of Neural Transmission 2001-01, Vol.108 (4), p.459-473 |
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| container_title | Journal of Neural Transmission |
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| creator | HARTBAUER, M HUTTER-PAIER, B SKOFITSCH, G WINDISCH, M |
| description | Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides ( |
| doi_str_mv | 10.1007/s007020170067 |
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It consists of approximately 25% of low molecular weight peptides (<10k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content. In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin. To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control. Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply.</description><identifier>ISSN: 0300-9564</identifier><identifier>EISSN: 1435-1463</identifier><identifier>DOI: 10.1007/s007020170067</identifier><identifier>PMID: 11475013</identifier><identifier>CODEN: JNTMAH</identifier><language>eng</language><publisher>Wien: Springer</publisher><subject>Amino Acids - pharmacology ; Animals ; Apoptosis - drug effects ; Biological and medical sciences ; Blood Proteins - pharmacology ; Cell Survival - drug effects ; Cells, Cultured ; Cerebral Cortex - cytology ; Chick Embryo ; Dose-Response Relationship, Drug ; In Situ Nick-End Labeling ; Medical sciences ; Neurons - cytology ; Neurons - drug effects ; Neuropharmacology ; Neuroprotective agent ; Neuroprotective Agents - pharmacology ; Pharmacology. Drug treatments</subject><ispartof>Journal of Neural Transmission, 2001-01, Vol.108 (4), p.459-473</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c317t-3b0c1b6a891173fc7af4f26d97badbc5c666570347029f8cdf1c45d5c6959c073</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=918393$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11475013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HARTBAUER, M</creatorcontrib><creatorcontrib>HUTTER-PAIER, B</creatorcontrib><creatorcontrib>SKOFITSCH, G</creatorcontrib><creatorcontrib>WINDISCH, M</creatorcontrib><title>Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons</title><title>Journal of Neural Transmission</title><addtitle>J Neural Transm (Vienna)</addtitle><description>Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (<10k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content. In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin. To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control. Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply.</description><subject>Amino Acids - pharmacology</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood Proteins - pharmacology</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - cytology</subject><subject>Chick Embryo</subject><subject>Dose-Response Relationship, Drug</subject><subject>In Situ Nick-End Labeling</subject><subject>Medical sciences</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><issn>0300-9564</issn><issn>1435-1463</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1v2zAMxYVhxZKmO-5aCBjQmzsysqzoGAT9Agr0sp4NmZYSb47lSfIh_321xWixCwmQPz7wPca-IdwigPoRc4E1oAKo1Ce2xFLIAstKfGZLEACFllW5YJcx_gIARLX5whaIpZKAYsnCdkidGf2YfOqIW-cspci94-lg-WjH1LU27POqDdOe72ywTfD9KXYD9wMfQ3c04cRp6tMU7L9De2zCyQ_5hA4d_ebkQ5Y2PR_sFPwQr9iFM320X-e-Yq_3dz93j8Xzy8PTbvtckECVCtEAYVOZjc5PC0fKuNKtq1arxrQNSaqqSioQZbav3YZah1TKNs-11ARKrNjNWXcM_s9kY6qPXSTb92awfoq1QpC41jKDxRmk4GMM1tWzrRqh_hty_V_Imb-ehafmaNsPek41A99nwMRs3AUzUBffOY0boYV4A0PkhZw</recordid><startdate>20010101</startdate><enddate>20010101</enddate><creator>HARTBAUER, M</creator><creator>HUTTER-PAIER, B</creator><creator>SKOFITSCH, G</creator><creator>WINDISCH, M</creator><general>Springer</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>7X8</scope></search><sort><creationdate>20010101</creationdate><title>Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons</title><author>HARTBAUER, M ; HUTTER-PAIER, B ; SKOFITSCH, G ; WINDISCH, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317t-3b0c1b6a891173fc7af4f26d97badbc5c666570347029f8cdf1c45d5c6959c073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acids - pharmacology</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood Proteins - pharmacology</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - cytology</topic><topic>Chick Embryo</topic><topic>Dose-Response Relationship, Drug</topic><topic>In Situ Nick-End Labeling</topic><topic>Medical sciences</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HARTBAUER, M</creatorcontrib><creatorcontrib>HUTTER-PAIER, B</creatorcontrib><creatorcontrib>SKOFITSCH, G</creatorcontrib><creatorcontrib>WINDISCH, M</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>MEDLINE - Academic</collection><jtitle>Journal of Neural Transmission</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HARTBAUER, M</au><au>HUTTER-PAIER, B</au><au>SKOFITSCH, G</au><au>WINDISCH, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons</atitle><jtitle>Journal of Neural Transmission</jtitle><addtitle>J Neural Transm (Vienna)</addtitle><date>2001-01-01</date><risdate>2001</risdate><volume>108</volume><issue>4</issue><spage>459</spage><epage>473</epage><pages>459-473</pages><issn>0300-9564</issn><eissn>1435-1463</eissn><coden>JNTMAH</coden><abstract>Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (<10k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content. In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin. To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control. Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply.</abstract><cop>Wien</cop><cop>New York, NY</cop><pub>Springer</pub><pmid>11475013</pmid><doi>10.1007/s007020170067</doi><tpages>15</tpages></addata></record> |
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| subjects | Amino Acids - pharmacology Animals Apoptosis - drug effects Biological and medical sciences Blood Proteins - pharmacology Cell Survival - drug effects Cells, Cultured Cerebral Cortex - cytology Chick Embryo Dose-Response Relationship, Drug In Situ Nick-End Labeling Medical sciences Neurons - cytology Neurons - drug effects Neuropharmacology Neuroprotective agent Neuroprotective Agents - pharmacology Pharmacology. Drug treatments |
| title | Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons |
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