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...

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Veröffentlicht in:Journal of comparative neurology (1911) 2013-10, Vol.521 (15), p.3508-3523
Hauptverfasser: Spiegel, Amy M., Koh, Ming Teng, Vogt, Nicholas M., Rapp, Peter R., Gallagher, Michela
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container_issue 15
container_start_page 3508
container_title Journal of comparative neurology (1911)
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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.
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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. 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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. 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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>
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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
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