Effect of PPF and ALCAR on the Induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain
Amyloidogenic processing of β-amyloid precursor protein (APP) leading to Aβ accumulation is critical in Alzheimer’s disease (AD). Aβ leads to pre-synaptic molecular changes in hippocampus of the AD mutant transgenic mouse model Tg2576 prior to plaque formation. Since NGF is critical to neuronal grow...
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description | Amyloidogenic processing of β-amyloid precursor protein (APP) leading to Aβ accumulation is critical in Alzheimer’s disease (AD). Aβ leads to pre-synaptic molecular changes in hippocampus of the AD mutant transgenic mouse model Tg2576 prior to plaque formation. Since NGF is critical to neuronal growth and is involved in regulating APP processing, we tested the hypothesis that NGF expression is altered early in this model of AD. We measured APP products and mRNAs for NGF and its low-affinity receptor p75 in 10-month-old Tg2576 whole brain after dietary propentofylline (PPF) or acetyl-
l-carnitine (ALCAR) for 4 weeks to induce NGF- or p75-expression, respectively. The results (all
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doi_str_mv | 10.1016/S0197-0186(03)00006-8 |
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l-carnitine (ALCAR) for 4 weeks to induce NGF- or p75-expression, respectively. The results (all
P<0.0002) show that compared to wild-type or littermate controls, the transgene leads to decreases of 44% in NGF-mRNA, 25% in p75-mRNA, 64% in sAPPα, and 21-fold increases in Aβ40/42. PPF increased NGF-mRNA by 20% and sAPPα by 42% while decreasing Aβ40/42 by 45/48%, with no effect on p75-mRNA in Tg animals. ALCAR increased p75-mRNA by 16% and decreased Aβ40/42 by 46/26% with no significant effect on sAPPα or NGF-mRNA in Tg animals. The results indicate that NGF expression is reduced early in the Tg brain, that this reduction potentiates further Aβ formation in a vicious cycle, and that inducing NGF shifts the balance toward secretory processing of APP. To a lesser extent, p75 decreases Aβ peptides, possibly via peptidases since sAPPα level is not changed.</description><identifier>ISSN: 0197-0186</identifier><identifier>EISSN: 1872-9754</identifier><identifier>DOI: 10.1016/S0197-0186(03)00006-8</identifier><identifier>PMID: 12689602</identifier><identifier>CODEN: NEUIDS</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Acetylcarnitine ; Acetylcarnitine - physiology ; Alzheimer’s disease ; Amyloid ; Amyloid beta-Protein Precursor - metabolism ; Amyloid beta-Protein Precursor - physiology ; Animals ; APP processing ; Base Sequence ; Biological and medical sciences ; Brain - metabolism ; cRTPCR ; DNA Primers ; ELISA ; Enzyme-Linked Immunosorbent Assay ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - physiology ; Mice ; Mice, Transgenic ; Nerve Growth Factor - genetics ; Polymerase Chain Reaction ; propentofylline ; Protein Processing, Post-Translational ; Receptor, Nerve Growth Factor ; Receptors, Nerve Growth Factor - genetics ; RNA, Messenger - genetics ; Septohippocampal</subject><ispartof>Neurochemistry international, 2003-08, Vol.43 (3), p.225-233</ispartof><rights>2003</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-4a013a8dbc071f3d6a128db4b0afb51b1261bc167bf89950024698b59628416f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0197018603000068$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14736169$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12689602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chauhan, N.B</creatorcontrib><creatorcontrib>Siegel, G.J</creatorcontrib><title>Effect of PPF and ALCAR on the Induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain</title><title>Neurochemistry international</title><addtitle>Neurochem Int</addtitle><description>Amyloidogenic processing of β-amyloid precursor protein (APP) leading to Aβ accumulation is critical in Alzheimer’s disease (AD). Aβ leads to pre-synaptic molecular changes in hippocampus of the AD mutant transgenic mouse model Tg2576 prior to plaque formation. Since NGF is critical to neuronal growth and is involved in regulating APP processing, we tested the hypothesis that NGF expression is altered early in this model of AD. We measured APP products and mRNAs for NGF and its low-affinity receptor p75 in 10-month-old Tg2576 whole brain after dietary propentofylline (PPF) or acetyl-
l-carnitine (ALCAR) for 4 weeks to induce NGF- or p75-expression, respectively. The results (all
P<0.0002) show that compared to wild-type or littermate controls, the transgene leads to decreases of 44% in NGF-mRNA, 25% in p75-mRNA, 64% in sAPPα, and 21-fold increases in Aβ40/42. PPF increased NGF-mRNA by 20% and sAPPα by 42% while decreasing Aβ40/42 by 45/48%, with no effect on p75-mRNA in Tg animals. ALCAR increased p75-mRNA by 16% and decreased Aβ40/42 by 46/26% with no significant effect on sAPPα or NGF-mRNA in Tg animals. The results indicate that NGF expression is reduced early in the Tg brain, that this reduction potentiates further Aβ formation in a vicious cycle, and that inducing NGF shifts the balance toward secretory processing of APP. To a lesser extent, p75 decreases Aβ peptides, possibly via peptidases since sAPPα level is not changed.</description><subject>Acetylcarnitine</subject><subject>Acetylcarnitine - physiology</subject><subject>Alzheimer’s disease</subject><subject>Amyloid</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid beta-Protein Precursor - physiology</subject><subject>Animals</subject><subject>APP processing</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>cRTPCR</subject><subject>DNA Primers</subject><subject>ELISA</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Nerve Growth Factor - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>propentofylline</subject><subject>Protein Processing, Post-Translational</subject><subject>Receptor, Nerve Growth Factor</subject><subject>Receptors, Nerve Growth Factor - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>Septohippocampal</subject><issn>0197-0186</issn><issn>1872-9754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS0EoqHwE0DegMpiwNczfq3QKGpKpahEpawt22MXo8ST2hMk_n2dh-iy3lhH_q7v0TkIvQfyBQjwrz8JKNEQkPyCtJ9JPbyRL9AMpKCNEqx7iWb_kTP0ppQ_lRGKsNfoDCiXihM6Q-4yBO8mPAa8Wi2wSQPul_P-Fo8JT789vk7Dzk2xqkrcXC2aA7IVrNnc3vQHUd_61Qpv8-h8KTHd45jw3T1lgmObTUxv0atg1sW_O93n6Nfi8m7-vVn-uLqe98vGdZROTWcItEYO1hEBoR24AVpVZ4kJloGtpsE64MIGqRQjhHZcScsUp7IDHtpz9On4b7XysPNl0ptYnF-vTfLjrmjRgpCdZM-CIBUIpVQF2RF0eSwl-6C3OW5M_qeB6H0N-lCD3mesSasPNWhZ5z6cFuzsxg9PU6fcK_DxBJjizDpkk1wsT1wnWg58b-DbkfM1t7_RZ11c9Mn5IeZamx7G-IyVR7pZnp0</recordid><startdate>20030801</startdate><enddate>20030801</enddate><creator>Chauhan, N.B</creator><creator>Siegel, G.J</creator><general>Elsevier Ltd</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></search><sort><creationdate>20030801</creationdate><title>Effect of PPF and ALCAR on the Induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain</title><author>Chauhan, N.B ; Siegel, G.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-4a013a8dbc071f3d6a128db4b0afb51b1261bc167bf89950024698b59628416f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acetylcarnitine</topic><topic>Acetylcarnitine - physiology</topic><topic>Alzheimer’s disease</topic><topic>Amyloid</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid beta-Protein Precursor - physiology</topic><topic>Animals</topic><topic>APP processing</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>cRTPCR</topic><topic>DNA Primers</topic><topic>ELISA</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nerve Growth Factor - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>propentofylline</topic><topic>Protein Processing, Post-Translational</topic><topic>Receptor, Nerve Growth Factor</topic><topic>Receptors, Nerve Growth Factor - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>Septohippocampal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chauhan, N.B</creatorcontrib><creatorcontrib>Siegel, G.J</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><jtitle>Neurochemistry international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chauhan, N.B</au><au>Siegel, G.J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of PPF and ALCAR on the Induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain</atitle><jtitle>Neurochemistry international</jtitle><addtitle>Neurochem Int</addtitle><date>2003-08-01</date><risdate>2003</risdate><volume>43</volume><issue>3</issue><spage>225</spage><epage>233</epage><pages>225-233</pages><issn>0197-0186</issn><eissn>1872-9754</eissn><coden>NEUIDS</coden><abstract>Amyloidogenic processing of β-amyloid precursor protein (APP) leading to Aβ accumulation is critical in Alzheimer’s disease (AD). Aβ leads to pre-synaptic molecular changes in hippocampus of the AD mutant transgenic mouse model Tg2576 prior to plaque formation. Since NGF is critical to neuronal growth and is involved in regulating APP processing, we tested the hypothesis that NGF expression is altered early in this model of AD. We measured APP products and mRNAs for NGF and its low-affinity receptor p75 in 10-month-old Tg2576 whole brain after dietary propentofylline (PPF) or acetyl-
l-carnitine (ALCAR) for 4 weeks to induce NGF- or p75-expression, respectively. The results (all
P<0.0002) show that compared to wild-type or littermate controls, the transgene leads to decreases of 44% in NGF-mRNA, 25% in p75-mRNA, 64% in sAPPα, and 21-fold increases in Aβ40/42. PPF increased NGF-mRNA by 20% and sAPPα by 42% while decreasing Aβ40/42 by 45/48%, with no effect on p75-mRNA in Tg animals. ALCAR increased p75-mRNA by 16% and decreased Aβ40/42 by 46/26% with no significant effect on sAPPα or NGF-mRNA in Tg animals. The results indicate that NGF expression is reduced early in the Tg brain, that this reduction potentiates further Aβ formation in a vicious cycle, and that inducing NGF shifts the balance toward secretory processing of APP. To a lesser extent, p75 decreases Aβ peptides, possibly via peptidases since sAPPα level is not changed.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>12689602</pmid><doi>10.1016/S0197-0186(03)00006-8</doi><tpages>9</tpages></addata></record> |
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subjects | Acetylcarnitine Acetylcarnitine - physiology Alzheimer’s disease Amyloid Amyloid beta-Protein Precursor - metabolism Amyloid beta-Protein Precursor - physiology Animals APP processing Base Sequence Biological and medical sciences Brain - metabolism cRTPCR DNA Primers ELISA Enzyme-Linked Immunosorbent Assay Fundamental and applied biological sciences. Psychology Gene Expression Regulation - physiology Mice Mice, Transgenic Nerve Growth Factor - genetics Polymerase Chain Reaction propentofylline Protein Processing, Post-Translational Receptor, Nerve Growth Factor Receptors, Nerve Growth Factor - genetics RNA, Messenger - genetics Septohippocampal |
title | Effect of PPF and ALCAR on the Induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain |
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