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Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration.

Fang Y, Iu CY, Lui CN, Zou Y, Fung CK, Li HW, Xi N, Yung KK, Lai KW - Sci Rep (2014)

Bottom Line: Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale.A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration.The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong.

ABSTRACT
Glutamate-mediated neurodegeneration resulting from excessive activation of glutamate receptors is recognized as one of the major causes of various neurological disorders such as Alzheimer's and Huntington's diseases. However, the underlying mechanisms in the neurodegenerative process remain unidentified. Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale. Atomic force microscopy (AFM) is employed to measure the three-dimensional (3-D) topography and mechanical properties of live SH-SY5Y cells under stimulus of NMDA receptors. A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration. The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.

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Related in: MedlinePlus

Experimental curve of Young's modulus of SH-SY5Y cells versus duration of the 50 μM NMDA treatment and statistical comparison with the curve of Young's modulus of normal SH-SY5Y cells over the test period (60 minutes).Statistical analysis was conducted by SPSS using One-way ANOVA followed by Newman-Keuls post hoc test (**p<0.01). Data are represented as mean ± SEM.
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f6: Experimental curve of Young's modulus of SH-SY5Y cells versus duration of the 50 μM NMDA treatment and statistical comparison with the curve of Young's modulus of normal SH-SY5Y cells over the test period (60 minutes).Statistical analysis was conducted by SPSS using One-way ANOVA followed by Newman-Keuls post hoc test (**p<0.01). Data are represented as mean ± SEM.

Mentions: NMDA receptors are ion channels on the cytomembrane that mediate the transport of K+, Na+ and Ca2+, and the effect of NMDA receptors depends on the time of the NMDA receptors channel opening. Therefore, it is crucial to study the time course of the NMDA-receptors medicated neurodenegation. It is relatively difficult to apply conventional biological methods for monitoring the real time response of live neuronal cells. Here, AFM was employed to monitor the mechanical property and morphology of the neuronal cell over time. The Young's modulus of the SH-SY5Y neuronal cell before NMDA treatment was first recorded (the data as shown at 0 min in Fig. 6). After adding 50 μM NMDA to the SH-SY5Y neuronal cell, the Young's modulus was taken in 10 minutes time interval. The Young's modulus of SH-SY5Y neuronal cell was gradually increased with the time of the NMDA treatment, while the Young's modulus of the normal SH-SY5Y neuronal cell did not change significantly over the test period (Fig. 6).


Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration.

Fang Y, Iu CY, Lui CN, Zou Y, Fung CK, Li HW, Xi N, Yung KK, Lai KW - Sci Rep (2014)

Experimental curve of Young's modulus of SH-SY5Y cells versus duration of the 50 μM NMDA treatment and statistical comparison with the curve of Young's modulus of normal SH-SY5Y cells over the test period (60 minutes).Statistical analysis was conducted by SPSS using One-way ANOVA followed by Newman-Keuls post hoc test (**p<0.01). Data are represented as mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4233341&req=5

f6: Experimental curve of Young's modulus of SH-SY5Y cells versus duration of the 50 μM NMDA treatment and statistical comparison with the curve of Young's modulus of normal SH-SY5Y cells over the test period (60 minutes).Statistical analysis was conducted by SPSS using One-way ANOVA followed by Newman-Keuls post hoc test (**p<0.01). Data are represented as mean ± SEM.
Mentions: NMDA receptors are ion channels on the cytomembrane that mediate the transport of K+, Na+ and Ca2+, and the effect of NMDA receptors depends on the time of the NMDA receptors channel opening. Therefore, it is crucial to study the time course of the NMDA-receptors medicated neurodenegation. It is relatively difficult to apply conventional biological methods for monitoring the real time response of live neuronal cells. Here, AFM was employed to monitor the mechanical property and morphology of the neuronal cell over time. The Young's modulus of the SH-SY5Y neuronal cell before NMDA treatment was first recorded (the data as shown at 0 min in Fig. 6). After adding 50 μM NMDA to the SH-SY5Y neuronal cell, the Young's modulus was taken in 10 minutes time interval. The Young's modulus of SH-SY5Y neuronal cell was gradually increased with the time of the NMDA treatment, while the Young's modulus of the normal SH-SY5Y neuronal cell did not change significantly over the test period (Fig. 6).

Bottom Line: Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale.A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration.The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong.

ABSTRACT
Glutamate-mediated neurodegeneration resulting from excessive activation of glutamate receptors is recognized as one of the major causes of various neurological disorders such as Alzheimer's and Huntington's diseases. However, the underlying mechanisms in the neurodegenerative process remain unidentified. Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale. Atomic force microscopy (AFM) is employed to measure the three-dimensional (3-D) topography and mechanical properties of live SH-SY5Y cells under stimulus of NMDA receptors. A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration. The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.

Show MeSH
Related in: MedlinePlus