Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice
•Intrahippocampal CDNF protein or gene improved long-term memory in mice.•CDNF did not influence short-term memory, spontaneous activity or object neophobia.•CDNF did not significantly affect brain amyloid load or adult neurogenesis. Cerebral dopamine neurotrophic factor (CDNF) protects and repairs...
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| Veröffentlicht in: | Behavioural brain research 2015-09, Vol.291, p.1-11 |
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| creator | Kemppainen, Susanna Lindholm, Päivi Galli, Emilia Lahtinen, Hanna-Maija Koivisto, Henna Hämäläinen, Elina Saarma, Mart Tanila, Heikki |
| description | •Intrahippocampal CDNF protein or gene improved long-term memory in mice.•CDNF did not influence short-term memory, spontaneous activity or object neophobia.•CDNF did not significantly affect brain amyloid load or adult neurogenesis.
Cerebral dopamine neurotrophic factor (CDNF) protects and repairs dopamine neurons in animal models of Parkinson's disease, which motivated us to investigate its therapeutic effect in an animal model of Alzheimer's disease (AD). We employed an established APP/PS1 mouse model of AD and gave intrahippocampal injections of CDNF protein or CDNF transgene in an AAV2 viral vector to 1-year-old animals. We performed a behavioral test battery 2 weeks after the injections and collected tissue samples after the 3-week test period. Intrahippocampal CDNF-therapy improved long-term memory in both APP/PS1 mice and wild-type controls, but did not affect spontaneous exploration, object neophobia or early stages of spatial learning. The memory improvement was not associated with decreased brain amyloid load or enhanced hippocampal neurogenesis. Intracranial CDNF treatment has beneficial effects on long-term memory and is well tolerated. The CDNF molecular mechanisms of action on memory await further studies. |
| doi_str_mv | 10.1016/j.bbr.2015.05.002 |
| format | Article |
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Cerebral dopamine neurotrophic factor (CDNF) protects and repairs dopamine neurons in animal models of Parkinson's disease, which motivated us to investigate its therapeutic effect in an animal model of Alzheimer's disease (AD). We employed an established APP/PS1 mouse model of AD and gave intrahippocampal injections of CDNF protein or CDNF transgene in an AAV2 viral vector to 1-year-old animals. We performed a behavioral test battery 2 weeks after the injections and collected tissue samples after the 3-week test period. Intrahippocampal CDNF-therapy improved long-term memory in both APP/PS1 mice and wild-type controls, but did not affect spontaneous exploration, object neophobia or early stages of spatial learning. The memory improvement was not associated with decreased brain amyloid load or enhanced hippocampal neurogenesis. Intracranial CDNF treatment has beneficial effects on long-term memory and is well tolerated. The CDNF molecular mechanisms of action on memory await further studies.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2015.05.002</identifier><identifier>PMID: 25975173</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer Disease - psychology ; Alzheimer Disease - therapy ; Amyloid ; Amyloid - metabolism ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Animals ; Dependovirus - genetics ; Disease Models, Animal ; Female ; Gene therapy ; Genetic Therapy - methods ; Genetic Vectors ; Hippocampus - metabolism ; Hippocampus - pathology ; Humans ; Memory ; Memory Consolidation - physiology ; Memory, Long-Term - physiology ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Growth Factors - genetics ; Nerve Growth Factors - metabolism ; Neurogenesis - physiology ; Neurotrophic factor ; Presenilin-1 - genetics ; Presenilin-1 - metabolism ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Transgenic</subject><ispartof>Behavioural brain research, 2015-09, Vol.291, p.1-11</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-e1786f67bda6713445eaae65f5da06be871e75a283ebbe4251ac7a5f54ad9b893</citedby><cites>FETCH-LOGICAL-c386t-e1786f67bda6713445eaae65f5da06be871e75a283ebbe4251ac7a5f54ad9b893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbr.2015.05.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25975173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kemppainen, Susanna</creatorcontrib><creatorcontrib>Lindholm, Päivi</creatorcontrib><creatorcontrib>Galli, Emilia</creatorcontrib><creatorcontrib>Lahtinen, Hanna-Maija</creatorcontrib><creatorcontrib>Koivisto, Henna</creatorcontrib><creatorcontrib>Hämäläinen, Elina</creatorcontrib><creatorcontrib>Saarma, Mart</creatorcontrib><creatorcontrib>Tanila, Heikki</creatorcontrib><title>Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>•Intrahippocampal CDNF protein or gene improved long-term memory in mice.•CDNF did not influence short-term memory, spontaneous activity or object neophobia.•CDNF did not significantly affect brain amyloid load or adult neurogenesis.
Cerebral dopamine neurotrophic factor (CDNF) protects and repairs dopamine neurons in animal models of Parkinson's disease, which motivated us to investigate its therapeutic effect in an animal model of Alzheimer's disease (AD). We employed an established APP/PS1 mouse model of AD and gave intrahippocampal injections of CDNF protein or CDNF transgene in an AAV2 viral vector to 1-year-old animals. We performed a behavioral test battery 2 weeks after the injections and collected tissue samples after the 3-week test period. Intrahippocampal CDNF-therapy improved long-term memory in both APP/PS1 mice and wild-type controls, but did not affect spontaneous exploration, object neophobia or early stages of spatial learning. The memory improvement was not associated with decreased brain amyloid load or enhanced hippocampal neurogenesis. Intracranial CDNF treatment has beneficial effects on long-term memory and is well tolerated. The CDNF molecular mechanisms of action on memory await further studies.</description><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer Disease - psychology</subject><subject>Alzheimer Disease - therapy</subject><subject>Amyloid</subject><subject>Amyloid - metabolism</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Animals</subject><subject>Dependovirus - genetics</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Humans</subject><subject>Memory</subject><subject>Memory Consolidation - physiology</subject><subject>Memory, Long-Term - physiology</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Nerve Growth Factors - genetics</subject><subject>Nerve Growth Factors - metabolism</subject><subject>Neurogenesis - physiology</subject><subject>Neurotrophic factor</subject><subject>Presenilin-1 - genetics</subject><subject>Presenilin-1 - metabolism</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Transgenic</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxi0EokvhAbgg3-CSrZ3EdiJOqxUUpEqsBJwt_5lsvYrtYGdbLc_BA9dhC0eQRprD_L5v7PkQek3JmhLKrw5rrdO6JpStSSlSP0Er2om6Eqztn6JVYXjVNnV3gV7kfCCEtITR5-iiZr1gVDQr9GsLCXRSI7ZxUt4FwAGOKc4pTrfO4EGZOSbs_JTiHWQ8xrCvZkgee_AxnbALeLPbXe2-UjwnFfIeQpF5ZwD7aGF0YY83489bcB7S24yty6AyYJXxPYzj0ovFvRttNZ8m-K18iZ4Naszw6rFfou8fP3zbfqpuvlx_3m5uKtN0fK6Aio4PXGiruKBN2zJQCjgbmFWEa-gEBcFU3TWgNbQ1o8oIVcatsr3u-uYSvTv7ls_9OEKepXfZlFepAPGYJRUt78oORv6P8n45aNPUBaVn1KSYc4JBTsl5lU6SErnkJg-y5CaX3CQpRRbNm0f7o_Zg_yr-BFWA92cAyj3uHCSZjYNgwLoEZpY2un_YPwCXtqpr</recordid><startdate>20150915</startdate><enddate>20150915</enddate><creator>Kemppainen, Susanna</creator><creator>Lindholm, Päivi</creator><creator>Galli, Emilia</creator><creator>Lahtinen, Hanna-Maija</creator><creator>Koivisto, Henna</creator><creator>Hämäläinen, Elina</creator><creator>Saarma, Mart</creator><creator>Tanila, Heikki</creator><general>Elsevier B.V</general><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><scope>7QG</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20150915</creationdate><title>Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice</title><author>Kemppainen, Susanna ; Lindholm, Päivi ; Galli, Emilia ; Lahtinen, Hanna-Maija ; Koivisto, Henna ; Hämäläinen, Elina ; Saarma, Mart ; Tanila, Heikki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-e1786f67bda6713445eaae65f5da06be871e75a283ebbe4251ac7a5f54ad9b893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer Disease - psychology</topic><topic>Alzheimer Disease - therapy</topic><topic>Amyloid</topic><topic>Amyloid - metabolism</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Animals</topic><topic>Dependovirus - genetics</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Humans</topic><topic>Memory</topic><topic>Memory Consolidation - physiology</topic><topic>Memory, Long-Term - physiology</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Nerve Growth Factors - genetics</topic><topic>Nerve Growth Factors - metabolism</topic><topic>Neurogenesis - physiology</topic><topic>Neurotrophic factor</topic><topic>Presenilin-1 - genetics</topic><topic>Presenilin-1 - metabolism</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Transgenic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kemppainen, Susanna</creatorcontrib><creatorcontrib>Lindholm, Päivi</creatorcontrib><creatorcontrib>Galli, Emilia</creatorcontrib><creatorcontrib>Lahtinen, Hanna-Maija</creatorcontrib><creatorcontrib>Koivisto, Henna</creatorcontrib><creatorcontrib>Hämäläinen, Elina</creatorcontrib><creatorcontrib>Saarma, Mart</creatorcontrib><creatorcontrib>Tanila, Heikki</creatorcontrib><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><collection>Animal Behavior Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Behavioural brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kemppainen, Susanna</au><au>Lindholm, Päivi</au><au>Galli, Emilia</au><au>Lahtinen, Hanna-Maija</au><au>Koivisto, Henna</au><au>Hämäläinen, Elina</au><au>Saarma, Mart</au><au>Tanila, Heikki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice</atitle><jtitle>Behavioural brain research</jtitle><addtitle>Behav Brain Res</addtitle><date>2015-09-15</date><risdate>2015</risdate><volume>291</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0166-4328</issn><eissn>1872-7549</eissn><abstract>•Intrahippocampal CDNF protein or gene improved long-term memory in mice.•CDNF did not influence short-term memory, spontaneous activity or object neophobia.•CDNF did not significantly affect brain amyloid load or adult neurogenesis.
Cerebral dopamine neurotrophic factor (CDNF) protects and repairs dopamine neurons in animal models of Parkinson's disease, which motivated us to investigate its therapeutic effect in an animal model of Alzheimer's disease (AD). We employed an established APP/PS1 mouse model of AD and gave intrahippocampal injections of CDNF protein or CDNF transgene in an AAV2 viral vector to 1-year-old animals. We performed a behavioral test battery 2 weeks after the injections and collected tissue samples after the 3-week test period. Intrahippocampal CDNF-therapy improved long-term memory in both APP/PS1 mice and wild-type controls, but did not affect spontaneous exploration, object neophobia or early stages of spatial learning. The memory improvement was not associated with decreased brain amyloid load or enhanced hippocampal neurogenesis. Intracranial CDNF treatment has beneficial effects on long-term memory and is well tolerated. The CDNF molecular mechanisms of action on memory await further studies.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25975173</pmid><doi>10.1016/j.bbr.2015.05.002</doi><tpages>11</tpages></addata></record> |
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| subjects | Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer Disease - psychology Alzheimer Disease - therapy Amyloid Amyloid - metabolism Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Animals Dependovirus - genetics Disease Models, Animal Female Gene therapy Genetic Therapy - methods Genetic Vectors Hippocampus - metabolism Hippocampus - pathology Humans Memory Memory Consolidation - physiology Memory, Long-Term - physiology Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Nerve Growth Factors - genetics Nerve Growth Factors - metabolism Neurogenesis - physiology Neurotrophic factor Presenilin-1 - genetics Presenilin-1 - metabolism Recombinant Proteins - genetics Recombinant Proteins - metabolism Transgenic |
| title | Cerebral dopamine neurotrophic factor improves long-term memory in APP/PS1 transgenic mice modeling Alzheimer's disease as well as in wild-type mice |
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