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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

Decline in dendritic spine density in the frontal cortex and hippocampus of rats at 4 months after STZ injection. (a) Representative images of the dendritic spine of the pyramidal neurons in cortical layers II/III. (b) Representative images of the dendritic spine of the pyramidal neurons in the CA1 region of the hippocampus. (c) Dendritic spine density in the frontal cortex and hippocampus was measured (see Materials and Methods for procedure details). *P < 0.05, significant difference compared with the age-matched control rats; n = 4. (d) Representative images of synaptophysin expression in the frontal cortex using western blot analysis. (e) Representative images of synaptophysin expression in the hippocampus using western blot analysis. (f) Relative expression of synaptophysin in the frontal cortex and hippocampus was determined. *P < 0.05, significant difference compared with the age-matched control group; n = 4.
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fig5: Decline in dendritic spine density in the frontal cortex and hippocampus of rats at 4 months after STZ injection. (a) Representative images of the dendritic spine of the pyramidal neurons in cortical layers II/III. (b) Representative images of the dendritic spine of the pyramidal neurons in the CA1 region of the hippocampus. (c) Dendritic spine density in the frontal cortex and hippocampus was measured (see Materials and Methods for procedure details). *P < 0.05, significant difference compared with the age-matched control rats; n = 4. (d) Representative images of synaptophysin expression in the frontal cortex using western blot analysis. (e) Representative images of synaptophysin expression in the hippocampus using western blot analysis. (f) Relative expression of synaptophysin in the frontal cortex and hippocampus was determined. *P < 0.05, significant difference compared with the age-matched control group; n = 4.

Mentions: To evaluate the synaptic plasticity, dendritic spine density and SYN expression were measured. Results showed that the dendritic spine density of the frontal cortex decreased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched control rats (Figures 5(a) and 5(c)). Consistently, the synaptophysin expression of the frontal cortex was lower in the diabetic rats than in the control rats (Figures 5(d) and 5(f)). Similarly, the dendritic spine density of the hippocampus decreased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched rats (Figures 5(b) and 5(c)). The synaptophysin level in the hippocampal tissues decreased in the diabetic rats compared with that in the age-matched control rats (Figures 5(e) and 5(f)).


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)

Decline in dendritic spine density in the frontal cortex and hippocampus of rats at 4 months after STZ injection. (a) Representative images of the dendritic spine of the pyramidal neurons in cortical layers II/III. (b) Representative images of the dendritic spine of the pyramidal neurons in the CA1 region of the hippocampus. (c) Dendritic spine density in the frontal cortex and hippocampus was measured (see Materials and Methods for procedure details). *P < 0.05, significant difference compared with the age-matched control rats; n = 4. (d) Representative images of synaptophysin expression in the frontal cortex using western blot analysis. (e) Representative images of synaptophysin expression in the hippocampus using western blot analysis. (f) Relative expression of synaptophysin in the frontal cortex and hippocampus was determined. *P < 0.05, significant difference compared with the age-matched control group; n = 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4150474&req=5

fig5: Decline in dendritic spine density in the frontal cortex and hippocampus of rats at 4 months after STZ injection. (a) Representative images of the dendritic spine of the pyramidal neurons in cortical layers II/III. (b) Representative images of the dendritic spine of the pyramidal neurons in the CA1 region of the hippocampus. (c) Dendritic spine density in the frontal cortex and hippocampus was measured (see Materials and Methods for procedure details). *P < 0.05, significant difference compared with the age-matched control rats; n = 4. (d) Representative images of synaptophysin expression in the frontal cortex using western blot analysis. (e) Representative images of synaptophysin expression in the hippocampus using western blot analysis. (f) Relative expression of synaptophysin in the frontal cortex and hippocampus was determined. *P < 0.05, significant difference compared with the age-matched control group; n = 4.
Mentions: To evaluate the synaptic plasticity, dendritic spine density and SYN expression were measured. Results showed that the dendritic spine density of the frontal cortex decreased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched control rats (Figures 5(a) and 5(c)). Consistently, the synaptophysin expression of the frontal cortex was lower in the diabetic rats than in the control rats (Figures 5(d) and 5(f)). Similarly, the dendritic spine density of the hippocampus decreased in the diabetic rats at 4 months after STZ injection compared with that in the age-matched rats (Figures 5(b) and 5(c)). The synaptophysin level in the hippocampal tissues decreased in the diabetic rats compared with that in the age-matched control rats (Figures 5(e) and 5(f)).

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