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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

Aβ42 deposition in rat hippocampus at 4 months after STZ injection. (a) Representative images of Aβ42 immunoreaction in the frontal cortex: black square was magnified and shown in red square; blue arrow indicates the glial cells. (b) Representative images of Aβ42 immunoreaction in the hippocampus: black square was magnified and shown in red square, blue arrow indicates the glial cells, and black arrow indicates the neuron. (c) Aβ42 was quantified in soluble and insoluble fractions of the cortex by ELISA. (d) Aβ42 was quantified in soluble and insoluble fractions of the hippocampus by ELISA. *P < 0.05, significant difference compared with the age-matched control rats; n = 6.
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fig4: Aβ42 deposition in rat hippocampus at 4 months after STZ injection. (a) Representative images of Aβ42 immunoreaction in the frontal cortex: black square was magnified and shown in red square; blue arrow indicates the glial cells. (b) Representative images of Aβ42 immunoreaction in the hippocampus: black square was magnified and shown in red square, blue arrow indicates the glial cells, and black arrow indicates the neuron. (c) Aβ42 was quantified in soluble and insoluble fractions of the cortex by ELISA. (d) Aβ42 was quantified in soluble and insoluble fractions of the hippocampus by ELISA. *P < 0.05, significant difference compared with the age-matched control rats; n = 6.

Mentions: Aβ deposition is the hallmark characteristic in AD and AD-like brain aging; in the present study,Aβ deposition was analysis. Immunohistochemistry revealed the presence of Aβ42 immunoreactivity in the frontal cortex (Figure 4(a)) and hippocampus (Figure 4(b)) of the diabetic rats at 4 months after STZ injection. Quantitative analysis of Aβ42 in the frontal cortex and hippocampal tissues by ELISA showed no significant difference in the soluble fraction of hippocampal tissues between the diabetic rats and age-matched control rats. However, the amount of Aβ42 in the insoluble fraction increased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched control rats (Figures 4(c) and 4(d)).


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)

Aβ42 deposition in rat hippocampus at 4 months after STZ injection. (a) Representative images of Aβ42 immunoreaction in the frontal cortex: black square was magnified and shown in red square; blue arrow indicates the glial cells. (b) Representative images of Aβ42 immunoreaction in the hippocampus: black square was magnified and shown in red square, blue arrow indicates the glial cells, and black arrow indicates the neuron. (c) Aβ42 was quantified in soluble and insoluble fractions of the cortex by ELISA. (d) Aβ42 was quantified in soluble and insoluble fractions of the hippocampus by ELISA. *P < 0.05, 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

fig4: Aβ42 deposition in rat hippocampus at 4 months after STZ injection. (a) Representative images of Aβ42 immunoreaction in the frontal cortex: black square was magnified and shown in red square; blue arrow indicates the glial cells. (b) Representative images of Aβ42 immunoreaction in the hippocampus: black square was magnified and shown in red square, blue arrow indicates the glial cells, and black arrow indicates the neuron. (c) Aβ42 was quantified in soluble and insoluble fractions of the cortex by ELISA. (d) Aβ42 was quantified in soluble and insoluble fractions of the hippocampus by ELISA. *P < 0.05, significant difference compared with the age-matched control rats; n = 6.
Mentions: Aβ deposition is the hallmark characteristic in AD and AD-like brain aging; in the present study,Aβ deposition was analysis. Immunohistochemistry revealed the presence of Aβ42 immunoreactivity in the frontal cortex (Figure 4(a)) and hippocampus (Figure 4(b)) of the diabetic rats at 4 months after STZ injection. Quantitative analysis of Aβ42 in the frontal cortex and hippocampal tissues by ELISA showed no significant difference in the soluble fraction of hippocampal tissues between the diabetic rats and age-matched control rats. However, the amount of Aβ42 in the insoluble fraction increased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched control rats (Figures 4(c) and 4(d)).

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