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Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.

Wang JQ, Yin J, Song YF, Zhang L, Ren YX, Wang DG, Gao LP, Jing YH - J Diabetes Res (2014)

Bottom Line: Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA.Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin.Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department and Blood Dialysis Center, Second Hospital of Lanzhou University, Lanzhou 730000, China.

ABSTRACT

Objective: Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear.

Research design and methods: Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box.

Results: Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats.

Conclusions: Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

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Related in: MedlinePlus

Fluoro-Jade C- (FJC-) positive cells were examined in the frontal cortex, hypothalamus, and hippocampus of rats at 4 months after STZ injection. (a) Representative images of FJC-positive cells in the frontal cortex. (c) Representative images of FJC-positive cells in the hypothalamus; 3V: third ventricle. (e) Representative images of FJC-positive cells in the hippocampus; DG: dentate gyrus. (b) Frontal cortex, (d) hypothalamus, and (f) hippocampus. FJC-positive cells were counted (see Materials and Methods for procedure details). **P < 0.01, significant difference compared with the age-matched control rats; n = 6.
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fig3: Fluoro-Jade C- (FJC-) positive cells were examined in the frontal cortex, hypothalamus, and hippocampus of rats at 4 months after STZ injection. (a) Representative images of FJC-positive cells in the frontal cortex. (c) Representative images of FJC-positive cells in the hypothalamus; 3V: third ventricle. (e) Representative images of FJC-positive cells in the hippocampus; DG: dentate gyrus. (b) Frontal cortex, (d) hypothalamus, and (f) hippocampus. FJC-positive cells were counted (see Materials and Methods for procedure details). **P < 0.01, significant difference compared with the age-matched control rats; n = 6.

Mentions: The effect of the persistent metabolic disorder on neuronal survival was determined by conducting FJC staining to evaluate the neurodegeneration in discrete brain regions. The number of FJC-positive cells was higher in the frontal cortex (Figures 3(a) and 3(b), 1570 ± 350), hypothalamus (Figures 3(c) and 3(d), 2800 ± 385), and hippocampus (Figures 3(e) and 3(f), 3235 ± 502) of the diabetic rats at 4 months after STZ injection than in those of the age-matched control rats.


Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.

Wang JQ, Yin J, Song YF, Zhang L, Ren YX, Wang DG, Gao LP, Jing YH - J Diabetes Res (2014)

Fluoro-Jade C- (FJC-) positive cells were examined in the frontal cortex, hypothalamus, and hippocampus of rats at 4 months after STZ injection. (a) Representative images of FJC-positive cells in the frontal cortex. (c) Representative images of FJC-positive cells in the hypothalamus; 3V: third ventricle. (e) Representative images of FJC-positive cells in the hippocampus; DG: dentate gyrus. (b) Frontal cortex, (d) hypothalamus, and (f) hippocampus. FJC-positive cells were counted (see Materials and Methods for procedure details). **P < 0.01, significant difference compared with the age-matched control rats; n = 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4150474&req=5

fig3: Fluoro-Jade C- (FJC-) positive cells were examined in the frontal cortex, hypothalamus, and hippocampus of rats at 4 months after STZ injection. (a) Representative images of FJC-positive cells in the frontal cortex. (c) Representative images of FJC-positive cells in the hypothalamus; 3V: third ventricle. (e) Representative images of FJC-positive cells in the hippocampus; DG: dentate gyrus. (b) Frontal cortex, (d) hypothalamus, and (f) hippocampus. FJC-positive cells were counted (see Materials and Methods for procedure details). **P < 0.01, significant difference compared with the age-matched control rats; n = 6.
Mentions: The effect of the persistent metabolic disorder on neuronal survival was determined by conducting FJC staining to evaluate the neurodegeneration in discrete brain regions. The number of FJC-positive cells was higher in the frontal cortex (Figures 3(a) and 3(b), 1570 ± 350), hypothalamus (Figures 3(c) and 3(d), 2800 ± 385), and hippocampus (Figures 3(e) and 3(f), 3235 ± 502) of the diabetic rats at 4 months after STZ injection than in those of the age-matched control rats.

Bottom Line: Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA.Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin.Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department and Blood Dialysis Center, Second Hospital of Lanzhou University, Lanzhou 730000, China.

ABSTRACT

Objective: Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear.

Research design and methods: Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box.

Results: Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats.

Conclusions: Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

Show MeSH
Related in: MedlinePlus