Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes

被引:105
作者
Alvarez, Edgardo O. [2 ]
Beauquis, Juan [1 ]
Revsin, Yanina [3 ]
Banzan, Arturo M. [2 ]
Roig, Paulina [1 ]
De Nicola, Alejandro F. [1 ,4 ]
Saravia, Flavia [1 ,4 ]
机构
[1] Consejo Nacl Invest Cient & Tecn, Natl Res Council, Inst Biol & Expt Med, RA-1428 Buenos Aires, DF, Argentina
[2] Natl Univ Cuyo, Fac Med Sci, Pharmacol Area, Mendoza, Argentina
[3] Leiden Univ, Med Ctr, LACDR, Div Med Pharmacol, Leiden, Netherlands
[4] Univ Buenos Aires, Fac Med, Dept Biochem, RA-1053 Buenos Aires, DF, Argentina
关键词
Type; 1; diabetes; Streptozotocin; Learning; Motivation; Hippocampus; Neurogenesis; Lipofuscin; ASYMMETRIC PLUS-MAZE; DENTATE GYRUS; HISTAMINE-RECEPTORS; SYNAPTIC PLASTICITY; SPONTANEOUS MODEL; NEUROGENESIS; MEMORY; RATS; MICE; NEURONS;
D O I
10.1016/j.bbr.2008.11.001
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:224 / 230
页数:7
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