Hilar interneuron vulnerability distinguishes aged rats with memory impairment
ABSTRACT Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model i...
Gespeichert in:
Veröffentlicht in: | Journal of comparative neurology (1911) 2013-10, Vol.521 (15), p.3508-3523 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 3523 |
---|---|
container_issue | 15 |
container_start_page | 3508 |
container_title | Journal of comparative neurology (1911) |
container_volume | 521 |
creator | Spiegel, Amy M. Koh, Ming Teng Vogt, Nicholas M. Rapp, Peter R. Gallagher, Michela |
description | ABSTRACT
Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.
By using stereological quantification, we show that a loss in glutamic acid decarboxylase‐67 (GAD67) and somatostatin (SOM)‐immunopositive neuron numbers in the hilar region of the dentate gyrus is associated with age‐related memory impairment in male Long‐Evans rats. The decline in SOM‐positive hilar neuron numbers likely reflects a loss of target protein rather than neuron death, because treatment with the antiepileptic levetiracetam fully restores hilar SOM expression in aged memory‐impaired rats. |
doi_str_mv | 10.1002/cne.23367 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4801143</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1433270908</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4817-2950bf0be127ffb43ee6837a148816790344fdd00cbcb0572bda59fde6a46dac3</originalsourceid><addsrcrecordid>eNp1kUtP20AUhUeoFaTAgj9QWeqGLgzzyjw2lVBEk0ooCAnIcjS2r5Oh9jjM2ND8-w4NRG0lVndxvnvuuToInRB8RjCm56WHM8qYkHtoRLAWuVaCfECjpJFcayEP0KcYHzDGWjO1jw4ok1xzxUZoPnONDZnzPQQPQ-h89jQ0HoItXOP6TVa52Du_HFxcQczsEqos2D5mz65fZS20Xdhkrl1bF1rw_RH6WNsmwvHrPER33y9vJ7P86nr6Y3JxlZdcEZlTPcZFjQsgVNZ1wRmAUExawpUiQmrMOK-rCuOyKAs8lrSo7FjXFQjLRWVLdoi-bX3XQ9FCVabTwTZmHVxrw8Z01pl_Fe9WZtk9Ga4wIZwlg9NXg9A9DhB707pYQtNYD90QzQtDJdZYJfTLf-hDNwSf3ksUFZrKFD1RX7dUGboYA9S7MASbl5ZMasn8aSmxn_9OvyPfaknA-RZ4dg1s3ncyk_nlm2W-3Uh1wa_dhg0_TVLl2CzmU3OvFov57c3UzNhvoKStVA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1426927837</pqid></control><display><type>article</type><title>Hilar interneuron vulnerability distinguishes aged rats with memory impairment</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Spiegel, Amy M. ; Koh, Ming Teng ; Vogt, Nicholas M. ; Rapp, Peter R. ; Gallagher, Michela</creator><creatorcontrib>Spiegel, Amy M. ; Koh, Ming Teng ; Vogt, Nicholas M. ; Rapp, Peter R. ; Gallagher, Michela</creatorcontrib><description>ABSTRACT
Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.
By using stereological quantification, we show that a loss in glutamic acid decarboxylase‐67 (GAD67) and somatostatin (SOM)‐immunopositive neuron numbers in the hilar region of the dentate gyrus is associated with age‐related memory impairment in male Long‐Evans rats. The decline in SOM‐positive hilar neuron numbers likely reflects a loss of target protein rather than neuron death, because treatment with the antiepileptic levetiracetam fully restores hilar SOM expression in aged memory‐impaired rats.</description><identifier>ISSN: 0021-9967</identifier><identifier>EISSN: 1096-9861</identifier><identifier>DOI: 10.1002/cne.23367</identifier><identifier>PMID: 23749483</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Aging - physiology ; Animals ; Antigens, Nuclear - metabolism ; Behavior, Animal - physiology ; CA3 Region, Hippocampal - cytology ; CA3 Region, Hippocampal - physiology ; Cell Count ; Cognition - physiology ; Glutamate Decarboxylase - metabolism ; hippocampus ; Hippocampus - growth & development ; Hippocampus - pathology ; Hippocampus - physiology ; Imaging, Three-Dimensional ; Immunohistochemistry ; interneuron ; Interneurons - pathology ; Interneurons - physiology ; Levetiracetam ; Male ; Memory Disorders - pathology ; Nerve Tissue Proteins - metabolism ; neuropeptide Y ; Neuropeptide Y - metabolism ; Nootropic Agents - pharmacology ; Perfusion ; Piracetam - analogs & derivatives ; Piracetam - pharmacology ; Rats ; Rats, Long-Evans ; somatostatin ; Somatostatin - metabolism ; stereology</subject><ispartof>Journal of comparative neurology (1911), 2013-10, Vol.521 (15), p.3508-3523</ispartof><rights>Copyright © 2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4817-2950bf0be127ffb43ee6837a148816790344fdd00cbcb0572bda59fde6a46dac3</citedby><cites>FETCH-LOGICAL-c4817-2950bf0be127ffb43ee6837a148816790344fdd00cbcb0572bda59fde6a46dac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcne.23367$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcne.23367$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23749483$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spiegel, Amy M.</creatorcontrib><creatorcontrib>Koh, Ming Teng</creatorcontrib><creatorcontrib>Vogt, Nicholas M.</creatorcontrib><creatorcontrib>Rapp, Peter R.</creatorcontrib><creatorcontrib>Gallagher, Michela</creatorcontrib><title>Hilar interneuron vulnerability distinguishes aged rats with memory impairment</title><title>Journal of comparative neurology (1911)</title><addtitle>J. Comp. Neurol</addtitle><description>ABSTRACT
Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.
By using stereological quantification, we show that a loss in glutamic acid decarboxylase‐67 (GAD67) and somatostatin (SOM)‐immunopositive neuron numbers in the hilar region of the dentate gyrus is associated with age‐related memory impairment in male Long‐Evans rats. The decline in SOM‐positive hilar neuron numbers likely reflects a loss of target protein rather than neuron death, because treatment with the antiepileptic levetiracetam fully restores hilar SOM expression in aged memory‐impaired rats.</description><subject>Aging - physiology</subject><subject>Animals</subject><subject>Antigens, Nuclear - metabolism</subject><subject>Behavior, Animal - physiology</subject><subject>CA3 Region, Hippocampal - cytology</subject><subject>CA3 Region, Hippocampal - physiology</subject><subject>Cell Count</subject><subject>Cognition - physiology</subject><subject>Glutamate Decarboxylase - metabolism</subject><subject>hippocampus</subject><subject>Hippocampus - growth & development</subject><subject>Hippocampus - pathology</subject><subject>Hippocampus - physiology</subject><subject>Imaging, Three-Dimensional</subject><subject>Immunohistochemistry</subject><subject>interneuron</subject><subject>Interneurons - pathology</subject><subject>Interneurons - physiology</subject><subject>Levetiracetam</subject><subject>Male</subject><subject>Memory Disorders - pathology</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>neuropeptide Y</subject><subject>Neuropeptide Y - metabolism</subject><subject>Nootropic Agents - pharmacology</subject><subject>Perfusion</subject><subject>Piracetam - analogs & derivatives</subject><subject>Piracetam - pharmacology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>somatostatin</subject><subject>Somatostatin - metabolism</subject><subject>stereology</subject><issn>0021-9967</issn><issn>1096-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtP20AUhUeoFaTAgj9QWeqGLgzzyjw2lVBEk0ooCAnIcjS2r5Oh9jjM2ND8-w4NRG0lVndxvnvuuToInRB8RjCm56WHM8qYkHtoRLAWuVaCfECjpJFcayEP0KcYHzDGWjO1jw4ok1xzxUZoPnONDZnzPQQPQ-h89jQ0HoItXOP6TVa52Du_HFxcQczsEqos2D5mz65fZS20Xdhkrl1bF1rw_RH6WNsmwvHrPER33y9vJ7P86nr6Y3JxlZdcEZlTPcZFjQsgVNZ1wRmAUExawpUiQmrMOK-rCuOyKAs8lrSo7FjXFQjLRWVLdoi-bX3XQ9FCVabTwTZmHVxrw8Z01pl_Fe9WZtk9Ga4wIZwlg9NXg9A9DhB707pYQtNYD90QzQtDJdZYJfTLf-hDNwSf3ksUFZrKFD1RX7dUGboYA9S7MASbl5ZMasn8aSmxn_9OvyPfaknA-RZ4dg1s3ncyk_nlm2W-3Uh1wa_dhg0_TVLl2CzmU3OvFov57c3UzNhvoKStVA</recordid><startdate>20131015</startdate><enddate>20131015</enddate><creator>Spiegel, Amy M.</creator><creator>Koh, Ming Teng</creator><creator>Vogt, Nicholas M.</creator><creator>Rapp, Peter R.</creator><creator>Gallagher, Michela</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131015</creationdate><title>Hilar interneuron vulnerability distinguishes aged rats with memory impairment</title><author>Spiegel, Amy M. ; Koh, Ming Teng ; Vogt, Nicholas M. ; Rapp, Peter R. ; Gallagher, Michela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4817-2950bf0be127ffb43ee6837a148816790344fdd00cbcb0572bda59fde6a46dac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aging - physiology</topic><topic>Animals</topic><topic>Antigens, Nuclear - metabolism</topic><topic>Behavior, Animal - physiology</topic><topic>CA3 Region, Hippocampal - cytology</topic><topic>CA3 Region, Hippocampal - physiology</topic><topic>Cell Count</topic><topic>Cognition - physiology</topic><topic>Glutamate Decarboxylase - metabolism</topic><topic>hippocampus</topic><topic>Hippocampus - growth & development</topic><topic>Hippocampus - pathology</topic><topic>Hippocampus - physiology</topic><topic>Imaging, Three-Dimensional</topic><topic>Immunohistochemistry</topic><topic>interneuron</topic><topic>Interneurons - pathology</topic><topic>Interneurons - physiology</topic><topic>Levetiracetam</topic><topic>Male</topic><topic>Memory Disorders - pathology</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>neuropeptide Y</topic><topic>Neuropeptide Y - metabolism</topic><topic>Nootropic Agents - pharmacology</topic><topic>Perfusion</topic><topic>Piracetam - analogs & derivatives</topic><topic>Piracetam - pharmacology</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>somatostatin</topic><topic>Somatostatin - metabolism</topic><topic>stereology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spiegel, Amy M.</creatorcontrib><creatorcontrib>Koh, Ming Teng</creatorcontrib><creatorcontrib>Vogt, Nicholas M.</creatorcontrib><creatorcontrib>Rapp, Peter R.</creatorcontrib><creatorcontrib>Gallagher, Michela</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of comparative neurology (1911)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spiegel, Amy M.</au><au>Koh, Ming Teng</au><au>Vogt, Nicholas M.</au><au>Rapp, Peter R.</au><au>Gallagher, Michela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hilar interneuron vulnerability distinguishes aged rats with memory impairment</atitle><jtitle>Journal of comparative neurology (1911)</jtitle><addtitle>J. Comp. Neurol</addtitle><date>2013-10-15</date><risdate>2013</risdate><volume>521</volume><issue>15</issue><spage>3508</spage><epage>3523</epage><pages>3508-3523</pages><issn>0021-9967</issn><eissn>1096-9861</eissn><abstract>ABSTRACT
Hippocampal interneuron populations are reportedly vulnerable to normal aging. The relationship between interneuron network integrity and age‐related memory impairment, however, has not been tested directly. That question was addressed in the present study using a well‐characterized model in which outbred, aged, male Long‐Evans rats exhibit a spectrum of individual differences in hippocampal‐dependent memory. Selected interneuron populations in the hippocampus were visualized for stereological quantification with a panel of immunocytochemical markers, including glutamic acid decarboxylase‐67 (GAD67), somatostatin, and neuropeptide Y. The overall pattern of results was that, although the numbers of GAD67‐ and somatostatin‐positive interneurons declined with age across multiple fields of the hippocampus, alterations specifically related to the cognitive outcome of aging were observed exclusively in the hilus of the dentate gyrus. Because the total number of NeuN‐immunoreactive hilar neurons was unaffected, the decline observed with other markers likely reflects a loss of target protein rather than neuron death. In support of that interpretation, treatment with the atypical antiepileptic levetiracetam at a low dose shown previously to improve behavioral performance fully restored hilar SOM expression in aged, memory‐impaired rats. Age‐related decreases in GAD67‐ and somatostatin‐immunoreactive neuron number beyond the hilus were regionally selective and spared the CA1 field of the hippocampus entirely. Together these findings confirm the vulnerability of hippocampal interneurons to normal aging and highlight that the integrity of a specific subpopulation in the hilus is coupled with age‐related memory impairment. J. Comp. Neurol. 521:3508‐3523, 2013. © 2013 Wiley Periodicals, Inc.
By using stereological quantification, we show that a loss in glutamic acid decarboxylase‐67 (GAD67) and somatostatin (SOM)‐immunopositive neuron numbers in the hilar region of the dentate gyrus is associated with age‐related memory impairment in male Long‐Evans rats. The decline in SOM‐positive hilar neuron numbers likely reflects a loss of target protein rather than neuron death, because treatment with the antiepileptic levetiracetam fully restores hilar SOM expression in aged memory‐impaired rats.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23749483</pmid><doi>10.1002/cne.23367</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9967 |
ispartof | Journal of comparative neurology (1911), 2013-10, Vol.521 (15), p.3508-3523 |
issn | 0021-9967 1096-9861 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4801143 |
source | MEDLINE; Wiley Online Library All Journals |
subjects | Aging - physiology Animals Antigens, Nuclear - metabolism Behavior, Animal - physiology CA3 Region, Hippocampal - cytology CA3 Region, Hippocampal - physiology Cell Count Cognition - physiology Glutamate Decarboxylase - metabolism hippocampus Hippocampus - growth & development Hippocampus - pathology Hippocampus - physiology Imaging, Three-Dimensional Immunohistochemistry interneuron Interneurons - pathology Interneurons - physiology Levetiracetam Male Memory Disorders - pathology Nerve Tissue Proteins - metabolism neuropeptide Y Neuropeptide Y - metabolism Nootropic Agents - pharmacology Perfusion Piracetam - analogs & derivatives Piracetam - pharmacology Rats Rats, Long-Evans somatostatin Somatostatin - metabolism stereology |
title | Hilar interneuron vulnerability distinguishes aged rats with memory impairment |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T06%3A48%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hilar%20interneuron%20vulnerability%20distinguishes%20aged%20rats%20with%20memory%20impairment&rft.jtitle=Journal%20of%20comparative%20neurology%20(1911)&rft.au=Spiegel,%20Amy%20M.&rft.date=2013-10-15&rft.volume=521&rft.issue=15&rft.spage=3508&rft.epage=3523&rft.pages=3508-3523&rft.issn=0021-9967&rft.eissn=1096-9861&rft_id=info:doi/10.1002/cne.23367&rft_dat=%3Cproquest_pubme%3E1433270908%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1426927837&rft_id=info:pmid/23749483&rfr_iscdi=true |