Lab Anim Res.  2018 Dec;34(4):195-202. 10.5625/lar.2018.34.4.195.

Hyperglycemia aggravates decrease in alpha-synuclein expression in a middle cerebral artery occlusion model

• Kang JB
• Kim DK
• Park DJ
• Shah MA
• Kim MO
• Jung EJ
• Lee HS
• Koh PO

• KMID: 2459295
• DOI: http://doi.org/10.5625/lar.2018.34.4.195

Abstract

Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. α-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of α-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in α-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in α-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in α-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that α-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing α-synuclein expression.

Keyword

α-Synuclein; hyperglycemia; MCAO

MeSH Terms

alpha-Synuclein*
Animals
Blotting, Western
Brain
Brain Injuries
Brain Ischemia
Cell Death
Cerebral Cortex
Cerebral Infarction
Humans
Hyperglycemia*
Infarction, Middle Cerebral Artery*
Injections, Intraperitoneal
Male
Middle Cerebral Artery*
Neurodegenerative Diseases
Neurons
Neuroprotective Agents
Polymerase Chain Reaction
Rats, Sprague-Dawley
Risk Factors
Streptozocin
Stroke
Neuroprotective Agents
Streptozocin
alpha-Synuclein

Figure

• 

  Figure 1 Body weight (A), neurobehavioral scores (B) and representative photographs of TTC staining (C) in the cerebral cortices of non-diabetic + sham, diabetic + sham, non-diabetic + middle cerebral artery occlusion (MCAO), and diabetic + MCAO animals. The intact area is shown in red, while the ischemic area is in white. The percentage of ischemic lesion area was calculated as the ratio of the infarction area to the whole section area (D). Data (n=4) are shown as mean ± SEM. *P<0.05.

• 

  Figure 2 A proteomic analysis of α-synuclein expression in the cerebral cortices of non-diabetic + sham, diabetic + sham, non-diabetic + MCAO, and diabetic + MCAO animals. Circles indicate α-synuclein proteins spots. Mw and pI indicate molecular weight and isoelectrical point, respectively. Spot intensities were measured by PDQuest software. The spot intensities are reported as a ratio relative to those of non-diabetic + sham animals. Data (n=4) are shown as mean ± SEM. *P<0.05.

• 

  Figure 3 Western blot analysis of α-synuclein expression in the cerebral cortices of non-diabetic + sham, diabetic + sham, non-diabetic + MCAO, and diabetic + MCAO animals. Each lane represents an individual animal. Densitometric analysis is represented as a ratio of these protein intensities to actin intensity. Data (n=4) are shown as mean±SEM. *P<0.05.

• 

  Figure 4 Reverse transcription PCR analysis of α-synuclein expression in the cerebral cortices of non-diabetic + sham, diabetic + sham, non-diabetic + MCAO, and diabetic + MCAO animals. Each lane represents an individual animal. The band intensity of the RT-PCR product was normalized to that of the actin product. Data (n=4) are shown as mean±SEM. *P<0.05.

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