Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes
Type 1 diabetes (T1D) is accompanied by a “diabetic encephalopathy” including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment. In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both...
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| Veröffentlicht in: | Behavioural brain research 2009-03, Vol.198 (1), p.224-230 |
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| creator | Alvarez, Edgardo O. Beauquis, Juan Revsin, Yanina Banzan, Arturo M. Roig, Paulina De Nicola, Alejandro F. Saravia, Flavia |
| description | Type 1 diabetes (T1D) is accompanied by a “diabetic encephalopathy” including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment.
In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended. |
| doi_str_mv | 10.1016/j.bbr.2008.11.001 |
| format | Article |
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In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2008.11.001</identifier><identifier>PMID: 19041902</identifier><identifier>CODEN: BBREDI</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - toxicity ; Avoidance Learning - physiology ; Behavioral psychophysiology ; Biological and medical sciences ; Body Weight - physiology ; Cognition - physiology ; Dentate Gyrus - cytology ; Dentate Gyrus - metabolism ; Dentate Gyrus - pathology ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1 - pathology ; Diabetes Mellitus, Type 1 - physiopathology ; Diabetes. Impaired glucose tolerance ; Disease Models, Animal ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Exploratory Behavior - physiology ; Fundamental and applied biological sciences. Psychology ; Glucose - metabolism ; Glycosuria - diagnosis ; Hippocampus ; Hippocampus - pathology ; Hippocampus - physiopathology ; Immunohistochemistry ; Injections, Intraperitoneal ; Learning ; Lipofuscin ; Lipofuscin - metabolism ; Male ; Maze Learning - physiology ; Medical sciences ; Memory - physiology ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Microtubule-Associated Proteins - metabolism ; Motivation ; Neurogenesis ; Neurons - cytology ; Neurons - metabolism ; Neurons - pathology ; Neuropeptides - metabolism ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Streptozocin ; Streptozotocin ; Type 1 diabetes</subject><ispartof>Behavioural brain research, 2009-03, Vol.198 (1), p.224-230</ispartof><rights>2008 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-cdd2df2c311493373d8f61088d8e160b44422797eecae0b4aa6583e6f9a3635c3</citedby><cites>FETCH-LOGICAL-c478t-cdd2df2c311493373d8f61088d8e160b44422797eecae0b4aa6583e6f9a3635c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166432808006074$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21242930$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19041902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alvarez, Edgardo O.</creatorcontrib><creatorcontrib>Beauquis, Juan</creatorcontrib><creatorcontrib>Revsin, Yanina</creatorcontrib><creatorcontrib>Banzan, Arturo M.</creatorcontrib><creatorcontrib>Roig, Paulina</creatorcontrib><creatorcontrib>De Nicola, Alejandro F.</creatorcontrib><creatorcontrib>Saravia, Flavia</creatorcontrib><title>Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>Type 1 diabetes (T1D) is accompanied by a “diabetic encephalopathy” including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment.
In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - toxicity</subject><subject>Avoidance Learning - physiology</subject><subject>Behavioral psychophysiology</subject><subject>Biological and medical sciences</subject><subject>Body Weight - physiology</subject><subject>Cognition - physiology</subject><subject>Dentate Gyrus - cytology</subject><subject>Dentate Gyrus - metabolism</subject><subject>Dentate Gyrus - pathology</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Diabetes Mellitus, Type 1 - pathology</subject><subject>Diabetes Mellitus, Type 1 - physiopathology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Disease Models, Animal</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Exploratory Behavior - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose - metabolism</subject><subject>Glycosuria - diagnosis</subject><subject>Hippocampus</subject><subject>Hippocampus - pathology</subject><subject>Hippocampus - physiopathology</subject><subject>Immunohistochemistry</subject><subject>Injections, Intraperitoneal</subject><subject>Learning</subject><subject>Lipofuscin</subject><subject>Lipofuscin - metabolism</subject><subject>Male</subject><subject>Maze Learning - physiology</subject><subject>Medical sciences</subject><subject>Memory - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Fluorescence</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Motivation</subject><subject>Neurogenesis</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neuropeptides - metabolism</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychology. Psychophysiology</subject><subject>Streptozocin</subject><subject>Streptozotocin</subject><subject>Type 1 diabetes</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtP4zAQgC0EgvL4AVxQLnBL8NhO4ojTqmKXlUBc4Gw59qR1lTrBThH997hqxd72MBrN6JuHPkKugRZAobpfFW0bCkapLAAKSuGIzEDWLK9L0RyTWWKqXHAmz8h5jCtKqaAlnJIzaKhIwWbkZT4svJvcJ2Z2G7uNN5MbfKa9zZZuHAej16PuM7PUfoExcz7DrxGDW6OfUn_ajphBZp1uccJ4SU463Ue8OuQL8v778W3-lD-__vk7__WcG1HLKTfWMtsxwwFEw3nNrewqoFJaiVDRVgjBWN3UiEZjKrWuSsmx6hrNK14afkHu9nvHMHxsME5q7aLBvtceh01UjLKyrCRNIOxBE4YYA3ZqTL_rsFVA1c6hWqnkUO0cKgCVHKaZm8PyTbtG-2_iIC0BtwdAR6P7LmhvXPzhGDDBGr47_rDnMKn4dBhUNA69QesCmknZwf3njW9r6o53</recordid><startdate>20090302</startdate><enddate>20090302</enddate><creator>Alvarez, Edgardo O.</creator><creator>Beauquis, Juan</creator><creator>Revsin, Yanina</creator><creator>Banzan, Arturo M.</creator><creator>Roig, Paulina</creator><creator>De Nicola, Alejandro F.</creator><creator>Saravia, Flavia</creator><general>Elsevier B.V</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>7QG</scope><scope>7TK</scope></search><sort><creationdate>20090302</creationdate><title>Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes</title><author>Alvarez, Edgardo O. ; Beauquis, Juan ; Revsin, Yanina ; Banzan, Arturo M. ; Roig, Paulina ; De Nicola, Alejandro F. ; Saravia, Flavia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-cdd2df2c311493373d8f61088d8e160b44422797eecae0b4aa6583e6f9a3635c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - toxicity</topic><topic>Avoidance Learning - physiology</topic><topic>Behavioral psychophysiology</topic><topic>Biological and medical sciences</topic><topic>Body Weight - physiology</topic><topic>Cognition - physiology</topic><topic>Dentate Gyrus - cytology</topic><topic>Dentate Gyrus - metabolism</topic><topic>Dentate Gyrus - pathology</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Diabetes Mellitus, Type 1 - pathology</topic><topic>Diabetes Mellitus, Type 1 - physiopathology</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Disease Models, Animal</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Exploratory Behavior - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose - metabolism</topic><topic>Glycosuria - diagnosis</topic><topic>Hippocampus</topic><topic>Hippocampus - pathology</topic><topic>Hippocampus - physiopathology</topic><topic>Immunohistochemistry</topic><topic>Injections, Intraperitoneal</topic><topic>Learning</topic><topic>Lipofuscin</topic><topic>Lipofuscin - metabolism</topic><topic>Male</topic><topic>Maze Learning - physiology</topic><topic>Medical sciences</topic><topic>Memory - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Fluorescence</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Motivation</topic><topic>Neurogenesis</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neuropeptides - metabolism</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychology. Psychophysiology</topic><topic>Streptozocin</topic><topic>Streptozotocin</topic><topic>Type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alvarez, Edgardo O.</creatorcontrib><creatorcontrib>Beauquis, Juan</creatorcontrib><creatorcontrib>Revsin, Yanina</creatorcontrib><creatorcontrib>Banzan, Arturo M.</creatorcontrib><creatorcontrib>Roig, Paulina</creatorcontrib><creatorcontrib>De Nicola, Alejandro F.</creatorcontrib><creatorcontrib>Saravia, Flavia</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>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Behavioural brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alvarez, Edgardo O.</au><au>Beauquis, Juan</au><au>Revsin, Yanina</au><au>Banzan, Arturo M.</au><au>Roig, Paulina</au><au>De Nicola, Alejandro F.</au><au>Saravia, Flavia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes</atitle><jtitle>Behavioural brain research</jtitle><addtitle>Behav Brain Res</addtitle><date>2009-03-02</date><risdate>2009</risdate><volume>198</volume><issue>1</issue><spage>224</spage><epage>230</epage><pages>224-230</pages><issn>0166-4328</issn><eissn>1872-7549</eissn><coden>BBREDI</coden><abstract>Type 1 diabetes (T1D) is accompanied by a “diabetic encephalopathy” including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment.
In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended.</abstract><cop>Shannon</cop><pub>Elsevier B.V</pub><pmid>19041902</pmid><doi>10.1016/j.bbr.2008.11.001</doi><tpages>7</tpages></addata></record> |
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| ispartof | Behavioural brain research, 2009-03, Vol.198 (1), p.224-230 |
| issn | 0166-4328 1872-7549 |
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| subjects | Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - toxicity Avoidance Learning - physiology Behavioral psychophysiology Biological and medical sciences Body Weight - physiology Cognition - physiology Dentate Gyrus - cytology Dentate Gyrus - metabolism Dentate Gyrus - pathology Diabetes Mellitus, Experimental Diabetes Mellitus, Type 1 - pathology Diabetes Mellitus, Type 1 - physiopathology Diabetes. Impaired glucose tolerance Disease Models, Animal Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Exploratory Behavior - physiology Fundamental and applied biological sciences. Psychology Glucose - metabolism Glycosuria - diagnosis Hippocampus Hippocampus - pathology Hippocampus - physiopathology Immunohistochemistry Injections, Intraperitoneal Learning Lipofuscin Lipofuscin - metabolism Male Maze Learning - physiology Medical sciences Memory - physiology Mice Mice, Inbred C57BL Microscopy, Fluorescence Microtubule-Associated Proteins - metabolism Motivation Neurogenesis Neurons - cytology Neurons - metabolism Neurons - pathology Neuropeptides - metabolism Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Streptozocin Streptozotocin Type 1 diabetes |
| title | Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes |
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