Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.
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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.
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PubMed Central - PubMed
Affiliation: Nephrology Department and Blood Dialysis Center, Second Hospital of Lanzhou University, Lanzhou 730000, China.
ABSTRACT
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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. Related in: MedlinePlus |
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fig1: Metabolic parameters of rats at four consecutive months after STZ injection. (a) Body weight, (b) water absorption/24 h, (c) food absorption/24 h, (d) urine/24 h, (e) plasma glucose, (f) plasma triglyceride, (g) plasma cholesterol, (h) creatinine clear ratio. *P < 0.05 denotes significant difference compared with the age-matched control rats. **P < 0.01, significant difference compared with the age-matched control rats; n = 18. Mentions: The results of consecutive metabolic test showed that the body weight (Figure 1(a)) of the diabetic rats was reduced compared with that of the age-matched rats. This test also demonstrated that the water consumption (Figure 1(b)), food consumption (Figure 1(c)), and urine production (Figure 1(d)) of the diabetic rats increased compared with those of the age-matched rats. Consecutive plasma examination showed that the levels of glucose (Figure 1(e)), triglyceride (Figure 1(f)), and cholesterol (Figure 1(g)) were higher in the diabetic rats than in the age-matched rats. Moreover, CCR was higher in the diabetic rats than in the age-matched control rats; this result was more pronounced at 2 months after STZ injection, suggesting that the kidney function was normal and that muscle wasting increased in the diabetic rats (Figure 1(h)). |
View Article: PubMed Central - PubMed
Affiliation: Nephrology Department and Blood Dialysis Center, Second Hospital of Lanzhou University, Lanzhou 730000, China.
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.