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Expression of TRPC6 and BDNF in Cortical Lesions From Patients With Focal Cortical Dysplasia.

Zheng DH, Guo W, Sun FJ, Xu GZ, Zang ZL, Shu HF, Yang H - J. Neuropathol. Exp. Neurol. (2016)

Bottom Line: Focal cortical dysplasia (FCD) likely results from abnormal migration of neural progenitor cells originating from the subventricular zone.There was also greater expression of calmodulin-dependent kinase IV (CaMKIV), the downstream factor of TRPC6, in FCD lesions, suggesting that TRPC6 expression promoted dendritic growth and the development of dendritic spines and excitatory synapses via the CaMKIV-CREB pathway in FCD.Thus, overexpression of BDNF and TRPC6 and activation of the TRPC6 signal transduction pathway in cortical lesions of FCD patients may contribute to FC pathogenesis and epileptogenesis.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (D-HZ, F-J, G-ZX, Z-LZ, H-FS, HY), Chongqing, China; Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University(WG), Xi'an, Shanxi, China; Department of Neurosurgery, General Hospital of Chengdu Military Region(H-FS), Chengdu, Sichuan, China.

No MeSH data available.


Related in: MedlinePlus

Expression of BDNF in FCD types Ia, IIa, IIb and normal CTX specimens. (A) Real-time polymerase chain reaction analysis of BDNF mRNA expression in CTX, FCDIa, FCDIIa, and FCDIIb (n = 10 in each group). Greater BDNF mRNA levels were observed in the FCDIa, FCDIIa, and FCDIIb samples versus the CTX samples. BDNF mRNA expression was significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05; **p < 0.01 versus CTX; #p < 0.05 versus FCDIa; ANOVA. (B) Representative immunoblots of BDNF in total homogenates from the FCDIa, FCDIIa, FCDIIb, and CTX samples. (C) Densitometric analyses of the Western blots. There was a significant increase in BDNF protein levels in the total homogenates from the FCDIa, FCDIIa, FCDIIb samples (n = 10 in each series) versus the CTX samples (n = 10). The expression of BDNF protein was also significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05, **p < 0.01 versus CTX, #p < 0.05 versus FCDIa; ANOVA. There was no significant difference BDNF expression levels between the FCDIIa and FCDIIb samples. (D–L) BDNF-immunoreactivity (-IR) in the CTX, FCDIa, FCDIIa, and FCDIIb samples. Representative immunohistochemical staining for BDNF in the control cortex (D), junction (E), and white matter (F) showing weak to moderate BDNF staining in neurons (arrows in D and E) and glia-like cells (arrowheads in E and F). In FCDI samples there is moderate to strong BDNF staining in neurons (arrows in G and H), including the microcolumns (insert in G) in the gray matter and heterotopic neurons (arrows in H) in the white matter. There was also moderate BDNF staining in glia-like cells (arrowheads in H). There is moderate to strong BDNF staining in FCDIIa samples in the DNs (arrows in I and J) and glia-like cells (arrowheads in J and insert in J). In FCDIIb samples there was moderate to strong BDNF-IR in the DNs (arrows in K, L and insert in K) and BCs (double-arrows in K, L and insert in L), along with moderate to strong staining in glia-like cells (arrowheads in K and L). Scale bars: D–F, H–J, L = 30 μm; G, K = 50 μm.
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nlw044-F5: Expression of BDNF in FCD types Ia, IIa, IIb and normal CTX specimens. (A) Real-time polymerase chain reaction analysis of BDNF mRNA expression in CTX, FCDIa, FCDIIa, and FCDIIb (n = 10 in each group). Greater BDNF mRNA levels were observed in the FCDIa, FCDIIa, and FCDIIb samples versus the CTX samples. BDNF mRNA expression was significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05; **p < 0.01 versus CTX; #p < 0.05 versus FCDIa; ANOVA. (B) Representative immunoblots of BDNF in total homogenates from the FCDIa, FCDIIa, FCDIIb, and CTX samples. (C) Densitometric analyses of the Western blots. There was a significant increase in BDNF protein levels in the total homogenates from the FCDIa, FCDIIa, FCDIIb samples (n = 10 in each series) versus the CTX samples (n = 10). The expression of BDNF protein was also significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05, **p < 0.01 versus CTX, #p < 0.05 versus FCDIa; ANOVA. There was no significant difference BDNF expression levels between the FCDIIa and FCDIIb samples. (D–L) BDNF-immunoreactivity (-IR) in the CTX, FCDIa, FCDIIa, and FCDIIb samples. Representative immunohistochemical staining for BDNF in the control cortex (D), junction (E), and white matter (F) showing weak to moderate BDNF staining in neurons (arrows in D and E) and glia-like cells (arrowheads in E and F). In FCDI samples there is moderate to strong BDNF staining in neurons (arrows in G and H), including the microcolumns (insert in G) in the gray matter and heterotopic neurons (arrows in H) in the white matter. There was also moderate BDNF staining in glia-like cells (arrowheads in H). There is moderate to strong BDNF staining in FCDIIa samples in the DNs (arrows in I and J) and glia-like cells (arrowheads in J and insert in J). In FCDIIb samples there was moderate to strong BDNF-IR in the DNs (arrows in K, L and insert in K) and BCs (double-arrows in K, L and insert in L), along with moderate to strong staining in glia-like cells (arrowheads in K and L). Scale bars: D–F, H–J, L = 30 μm; G, K = 50 μm.

Mentions: The expression of BDNF mRNA was evaluated by quantitative PCR in the FCD and CTX tissues; on average, a 1.5- to 2.5-fold increase was observed in the FCDIa, FCDIIa, and FCDIIb samples compared with the control cortex. BDNF mRNA levels were significantly increased in the FCDIIa and FCIIb tissues compared with the FCDIa tissues. There were no significant differences between FCDIIa and FCDIIb (Fig. 5A).FIGURE 5.


Expression of TRPC6 and BDNF in Cortical Lesions From Patients With Focal Cortical Dysplasia.

Zheng DH, Guo W, Sun FJ, Xu GZ, Zang ZL, Shu HF, Yang H - J. Neuropathol. Exp. Neurol. (2016)

Expression of BDNF in FCD types Ia, IIa, IIb and normal CTX specimens. (A) Real-time polymerase chain reaction analysis of BDNF mRNA expression in CTX, FCDIa, FCDIIa, and FCDIIb (n = 10 in each group). Greater BDNF mRNA levels were observed in the FCDIa, FCDIIa, and FCDIIb samples versus the CTX samples. BDNF mRNA expression was significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05; **p < 0.01 versus CTX; #p < 0.05 versus FCDIa; ANOVA. (B) Representative immunoblots of BDNF in total homogenates from the FCDIa, FCDIIa, FCDIIb, and CTX samples. (C) Densitometric analyses of the Western blots. There was a significant increase in BDNF protein levels in the total homogenates from the FCDIa, FCDIIa, FCDIIb samples (n = 10 in each series) versus the CTX samples (n = 10). The expression of BDNF protein was also significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05, **p < 0.01 versus CTX, #p < 0.05 versus FCDIa; ANOVA. There was no significant difference BDNF expression levels between the FCDIIa and FCDIIb samples. (D–L) BDNF-immunoreactivity (-IR) in the CTX, FCDIa, FCDIIa, and FCDIIb samples. Representative immunohistochemical staining for BDNF in the control cortex (D), junction (E), and white matter (F) showing weak to moderate BDNF staining in neurons (arrows in D and E) and glia-like cells (arrowheads in E and F). In FCDI samples there is moderate to strong BDNF staining in neurons (arrows in G and H), including the microcolumns (insert in G) in the gray matter and heterotopic neurons (arrows in H) in the white matter. There was also moderate BDNF staining in glia-like cells (arrowheads in H). There is moderate to strong BDNF staining in FCDIIa samples in the DNs (arrows in I and J) and glia-like cells (arrowheads in J and insert in J). In FCDIIb samples there was moderate to strong BDNF-IR in the DNs (arrows in K, L and insert in K) and BCs (double-arrows in K, L and insert in L), along with moderate to strong staining in glia-like cells (arrowheads in K and L). Scale bars: D–F, H–J, L = 30 μm; G, K = 50 μm.
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nlw044-F5: Expression of BDNF in FCD types Ia, IIa, IIb and normal CTX specimens. (A) Real-time polymerase chain reaction analysis of BDNF mRNA expression in CTX, FCDIa, FCDIIa, and FCDIIb (n = 10 in each group). Greater BDNF mRNA levels were observed in the FCDIa, FCDIIa, and FCDIIb samples versus the CTX samples. BDNF mRNA expression was significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05; **p < 0.01 versus CTX; #p < 0.05 versus FCDIa; ANOVA. (B) Representative immunoblots of BDNF in total homogenates from the FCDIa, FCDIIa, FCDIIb, and CTX samples. (C) Densitometric analyses of the Western blots. There was a significant increase in BDNF protein levels in the total homogenates from the FCDIa, FCDIIa, FCDIIb samples (n = 10 in each series) versus the CTX samples (n = 10). The expression of BDNF protein was also significantly greater in the FCDIIa and FCDIIb cortical lesions versus the FCDIa specimens. Error bars represent SE; *p < 0.05, **p < 0.01 versus CTX, #p < 0.05 versus FCDIa; ANOVA. There was no significant difference BDNF expression levels between the FCDIIa and FCDIIb samples. (D–L) BDNF-immunoreactivity (-IR) in the CTX, FCDIa, FCDIIa, and FCDIIb samples. Representative immunohistochemical staining for BDNF in the control cortex (D), junction (E), and white matter (F) showing weak to moderate BDNF staining in neurons (arrows in D and E) and glia-like cells (arrowheads in E and F). In FCDI samples there is moderate to strong BDNF staining in neurons (arrows in G and H), including the microcolumns (insert in G) in the gray matter and heterotopic neurons (arrows in H) in the white matter. There was also moderate BDNF staining in glia-like cells (arrowheads in H). There is moderate to strong BDNF staining in FCDIIa samples in the DNs (arrows in I and J) and glia-like cells (arrowheads in J and insert in J). In FCDIIb samples there was moderate to strong BDNF-IR in the DNs (arrows in K, L and insert in K) and BCs (double-arrows in K, L and insert in L), along with moderate to strong staining in glia-like cells (arrowheads in K and L). Scale bars: D–F, H–J, L = 30 μm; G, K = 50 μm.
Mentions: The expression of BDNF mRNA was evaluated by quantitative PCR in the FCD and CTX tissues; on average, a 1.5- to 2.5-fold increase was observed in the FCDIa, FCDIIa, and FCDIIb samples compared with the control cortex. BDNF mRNA levels were significantly increased in the FCDIIa and FCIIb tissues compared with the FCDIa tissues. There were no significant differences between FCDIIa and FCDIIb (Fig. 5A).FIGURE 5.

Bottom Line: Focal cortical dysplasia (FCD) likely results from abnormal migration of neural progenitor cells originating from the subventricular zone.There was also greater expression of calmodulin-dependent kinase IV (CaMKIV), the downstream factor of TRPC6, in FCD lesions, suggesting that TRPC6 expression promoted dendritic growth and the development of dendritic spines and excitatory synapses via the CaMKIV-CREB pathway in FCD.Thus, overexpression of BDNF and TRPC6 and activation of the TRPC6 signal transduction pathway in cortical lesions of FCD patients may contribute to FC pathogenesis and epileptogenesis.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (D-HZ, F-J, G-ZX, Z-LZ, H-FS, HY), Chongqing, China; Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University(WG), Xi'an, Shanxi, China; Department of Neurosurgery, General Hospital of Chengdu Military Region(H-FS), Chengdu, Sichuan, China.

No MeSH data available.


Related in: MedlinePlus