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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

Cell-specific distribution of TRPC6 in FCD types IIa and IIb. (A–K) TRPC6 in focal cortical dysplasia (FCD) type IIa (FCDIIa) samples. (A–C) There is moderate to strong TRPC6-immunoreactivity (-IR) in neurons, particularly the dysmorphic neurons (DNs), throughout the cortical layers (arrows in A and C) and in the white matter (arrows in B). Moderate to strong TRPC6-IR was also observed in glia-like cells in the FCDIIa samples (arrowheads in B). (Inset in C, D–K) Merged images show the colocalization of TRPC6 (green) with NeuN (red) (inset in C, D) in the DNs. Some scattered reactive astrocytes (GFAP-positive) are colabeled with TRPC6 (arrows in E–G). Double-label immunofluorescence shows that the TRPC6-positive DNs coexpressed either glutamate (H) or GABA (arrows in I); a few TRPC6-positive neurons colocalized with GAD65 (arrows in J) and GAD67 (arrows in K). (L–W) TRPC6 in FCD type IIb (FCDIIb) samples. There is moderate to strong TRPC6-IR in neurons, including dysmorphic neurons (DNs, arrows in L–N) and balloon cells (BCs, double-arrows in L and O). There is also moderate to strong TRPC6-IR in glia-like cells in the FCDIIb samples (arrowheads in M). (N–W) Merged images show colocalization of TRPC6 (green) with NeuN (red) (insert in N) in dystrophic neurons (DNs). TRPC6-positive BCs coexpress NeuN (insert in O) and glutamate (arrows in P). Double-label immunofluorescence showed that most of the TRPC6-positive BCs (double arrows) coexpressed glutamate (P). A few TRPC6-positive DNs and BCs coexpressed GABA, GAD65, and GAD67 (arrows in Q, R, S). TRPC6 was localized to a few GFAP-positive astrocytes (arrows in U–W) but not HLA-positive microglia (arrows in T). Scale bars: A, B, D–G, K–M = 30 μm; C, N, H–J, O = 10 μm; P–W = 20 μm.
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nlw044-F4: Cell-specific distribution of TRPC6 in FCD types IIa and IIb. (A–K) TRPC6 in focal cortical dysplasia (FCD) type IIa (FCDIIa) samples. (A–C) There is moderate to strong TRPC6-immunoreactivity (-IR) in neurons, particularly the dysmorphic neurons (DNs), throughout the cortical layers (arrows in A and C) and in the white matter (arrows in B). Moderate to strong TRPC6-IR was also observed in glia-like cells in the FCDIIa samples (arrowheads in B). (Inset in C, D–K) Merged images show the colocalization of TRPC6 (green) with NeuN (red) (inset in C, D) in the DNs. Some scattered reactive astrocytes (GFAP-positive) are colabeled with TRPC6 (arrows in E–G). Double-label immunofluorescence shows that the TRPC6-positive DNs coexpressed either glutamate (H) or GABA (arrows in I); a few TRPC6-positive neurons colocalized with GAD65 (arrows in J) and GAD67 (arrows in K). (L–W) TRPC6 in FCD type IIb (FCDIIb) samples. There is moderate to strong TRPC6-IR in neurons, including dysmorphic neurons (DNs, arrows in L–N) and balloon cells (BCs, double-arrows in L and O). There is also moderate to strong TRPC6-IR in glia-like cells in the FCDIIb samples (arrowheads in M). (N–W) Merged images show colocalization of TRPC6 (green) with NeuN (red) (insert in N) in dystrophic neurons (DNs). TRPC6-positive BCs coexpress NeuN (insert in O) and glutamate (arrows in P). Double-label immunofluorescence showed that most of the TRPC6-positive BCs (double arrows) coexpressed glutamate (P). A few TRPC6-positive DNs and BCs coexpressed GABA, GAD65, and GAD67 (arrows in Q, R, S). TRPC6 was localized to a few GFAP-positive astrocytes (arrows in U–W) but not HLA-positive microglia (arrows in T). Scale bars: A, B, D–G, K–M = 30 μm; C, N, H–J, O = 10 μm; P–W = 20 μm.

Mentions: In the FCDIIa samples, moderate to strong TRPC6 staining was detected in 74%  ±  4.3% of the DNs (n = 896) (Fig. 4A–C), of which 52% ± 4.3% exhibited strong staining (Fig. 4B, C). Strong staining was also displayed in cells exhibiting glial morphology (Fig. 4B). The intensity scores revealed prominent upregulation of TRPC6-immunoreactivity (-IR) in the FCDIIa specimens compared with the control samples and FCDIa tissues (Table 4). Double-labeling experiments revealed that most of the TRPC6-positive DNs coexpressed the neuronal marker NeuN (Fig. 4C inset, 4D). Most of these neurons were excitatory neurons (colabeled with glutamate) (Fig. 4H), and a few were inhibitory neurons (GAD65-, GAD67- and GABA-positive) (Fig. 4I–K). Coexpression of TRPC6 and GFAP was observed in some astrocytes (Fig. 4E–G), but almost none of the TRPC6-positive cells expressed the microglial marker HLA-DR (not shown).FIGURE 4.


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)

Cell-specific distribution of TRPC6 in FCD types IIa and IIb. (A–K) TRPC6 in focal cortical dysplasia (FCD) type IIa (FCDIIa) samples. (A–C) There is moderate to strong TRPC6-immunoreactivity (-IR) in neurons, particularly the dysmorphic neurons (DNs), throughout the cortical layers (arrows in A and C) and in the white matter (arrows in B). Moderate to strong TRPC6-IR was also observed in glia-like cells in the FCDIIa samples (arrowheads in B). (Inset in C, D–K) Merged images show the colocalization of TRPC6 (green) with NeuN (red) (inset in C, D) in the DNs. Some scattered reactive astrocytes (GFAP-positive) are colabeled with TRPC6 (arrows in E–G). Double-label immunofluorescence shows that the TRPC6-positive DNs coexpressed either glutamate (H) or GABA (arrows in I); a few TRPC6-positive neurons colocalized with GAD65 (arrows in J) and GAD67 (arrows in K). (L–W) TRPC6 in FCD type IIb (FCDIIb) samples. There is moderate to strong TRPC6-IR in neurons, including dysmorphic neurons (DNs, arrows in L–N) and balloon cells (BCs, double-arrows in L and O). There is also moderate to strong TRPC6-IR in glia-like cells in the FCDIIb samples (arrowheads in M). (N–W) Merged images show colocalization of TRPC6 (green) with NeuN (red) (insert in N) in dystrophic neurons (DNs). TRPC6-positive BCs coexpress NeuN (insert in O) and glutamate (arrows in P). Double-label immunofluorescence showed that most of the TRPC6-positive BCs (double arrows) coexpressed glutamate (P). A few TRPC6-positive DNs and BCs coexpressed GABA, GAD65, and GAD67 (arrows in Q, R, S). TRPC6 was localized to a few GFAP-positive astrocytes (arrows in U–W) but not HLA-positive microglia (arrows in T). Scale bars: A, B, D–G, K–M = 30 μm; C, N, H–J, O = 10 μm; P–W = 20 μm.
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nlw044-F4: Cell-specific distribution of TRPC6 in FCD types IIa and IIb. (A–K) TRPC6 in focal cortical dysplasia (FCD) type IIa (FCDIIa) samples. (A–C) There is moderate to strong TRPC6-immunoreactivity (-IR) in neurons, particularly the dysmorphic neurons (DNs), throughout the cortical layers (arrows in A and C) and in the white matter (arrows in B). Moderate to strong TRPC6-IR was also observed in glia-like cells in the FCDIIa samples (arrowheads in B). (Inset in C, D–K) Merged images show the colocalization of TRPC6 (green) with NeuN (red) (inset in C, D) in the DNs. Some scattered reactive astrocytes (GFAP-positive) are colabeled with TRPC6 (arrows in E–G). Double-label immunofluorescence shows that the TRPC6-positive DNs coexpressed either glutamate (H) or GABA (arrows in I); a few TRPC6-positive neurons colocalized with GAD65 (arrows in J) and GAD67 (arrows in K). (L–W) TRPC6 in FCD type IIb (FCDIIb) samples. There is moderate to strong TRPC6-IR in neurons, including dysmorphic neurons (DNs, arrows in L–N) and balloon cells (BCs, double-arrows in L and O). There is also moderate to strong TRPC6-IR in glia-like cells in the FCDIIb samples (arrowheads in M). (N–W) Merged images show colocalization of TRPC6 (green) with NeuN (red) (insert in N) in dystrophic neurons (DNs). TRPC6-positive BCs coexpress NeuN (insert in O) and glutamate (arrows in P). Double-label immunofluorescence showed that most of the TRPC6-positive BCs (double arrows) coexpressed glutamate (P). A few TRPC6-positive DNs and BCs coexpressed GABA, GAD65, and GAD67 (arrows in Q, R, S). TRPC6 was localized to a few GFAP-positive astrocytes (arrows in U–W) but not HLA-positive microglia (arrows in T). Scale bars: A, B, D–G, K–M = 30 μm; C, N, H–J, O = 10 μm; P–W = 20 μm.
Mentions: In the FCDIIa samples, moderate to strong TRPC6 staining was detected in 74%  ±  4.3% of the DNs (n = 896) (Fig. 4A–C), of which 52% ± 4.3% exhibited strong staining (Fig. 4B, C). Strong staining was also displayed in cells exhibiting glial morphology (Fig. 4B). The intensity scores revealed prominent upregulation of TRPC6-immunoreactivity (-IR) in the FCDIIa specimens compared with the control samples and FCDIa tissues (Table 4). Double-labeling experiments revealed that most of the TRPC6-positive DNs coexpressed the neuronal marker NeuN (Fig. 4C inset, 4D). Most of these neurons were excitatory neurons (colabeled with glutamate) (Fig. 4H), and a few were inhibitory neurons (GAD65-, GAD67- and GABA-positive) (Fig. 4I–K). Coexpression of TRPC6 and GFAP was observed in some astrocytes (Fig. 4E–G), but almost none of the TRPC6-positive cells expressed the microglial marker HLA-DR (not shown).FIGURE 4.

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