Expression of TRPC6 and BDNF in Cortical Lesions From Patients With Focal Cortical Dysplasia.
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.
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.
© Copyright Policy
License 1 - License 2
nlw044-F3: Cell-specific distribution of TRPC6 in CTX and FCDIa samples. (A–C) TRPC6 in the normal control cortex (CTX). Representative photomicrographs of immunohistochemical staining for TRPC6 in the control cortex (A), junction (B), and white matter (WM) (C), showing weak to moderate TRPC6 staining in neurons (arrows in A and B) and glia-like cells (arrowheads in B and C). (B inset, D–J) Double-label immunofluorescence showing TRPC6-positive cells in the control cortex. TRPC6 is shown in green; nuclei are stained with DAPI (blue). Antibodies against NeuN (B, inset) and glial ﬁbrillary acidic protein (GFAP) (D) were used to label neurons and astrocytes, respectively. Antibodies against glutamate, glutamic acid decarboxylase 65 (GAD65), glutamic acid decarboxylase 67 (GAD67), andγ-aminobutyric acid (GABA) were used to label glutamatergic neurons and GABAergic neurons and are also shown in red (E–J). The merged images are shown in yellow. The merged images show the colocalization of TRPC6 (green) with NeuN (red) in neurons (B, insert) and with GFAP (red) in astrocytes (arrows in D and inset). TRPC6 (green, E) was coexpressed with the excitatory neurotransmitter glutamate (red, F) in neurons of the CTX samples (arrows in E–G), suggesting that they are glutamatergic neurons. Merged images show that TRPC6 (green) is coexpressed with the inhibitory neurotransmitter GABA (red) (arrows in H), and with GAD65 and GAD67 (red) in neurons of the CTX samples (arrows in I and J), indicating that they are GABAergic neurons. (K–T) TRPC6 in focal cortical dysplasia (FCD) type Ia (FCDIa) samples. Representative photomicrographs of immunohistochemical staining for TRPC6 in the cortex (K), junction (L), and white matter (M) of FCDIa samples, showing moderate to strong TRPC6 staining in neurons (arrows in K–O), including the microcolumns (insert a in K), pyramidal neurons (N) and heterotopic neurons (arrows in M and O) in the white matter, and glia-like cells (arrowheads in L and M). (Insert b in K, M–T) Merged images show the colocalization of TRPC6 (green) and NeuN (red) in the pyramidal neurons (insert in N) and heterotopic neurons (insert in O) and the colocalization with GFAP (red) in astrocytes (P). Double-label immunofluorescence confirmed that the neurons in the microcolumns (insert b in K) and the heterotopic neurons (insert in M) are glutamatergic neurons. The merged images also show the colocalization of TRPC6 (green) with the marker of glutamatergic neurons, glutamate (red) (arrows in Q), and with the markers of GABAergic neurons, GABA (red) (R), GAD65 (red) (S), and GAD67 (red) (arrows in T), in neurons of the FCDIa samples. Scale bars: A–C, K–M = 30 μm; D–J, P, Q, T = 25 μm; N, O, R, S = 10 μm.
In the human control cortical autopsy specimens there was weak to moderate TRPC6 staining detected in the cell bodies and dendrites of neurons throughout the cortical layers (Fig. 3A, B); concurrently, weak to moderate staining was detected in the glia-like cells in the white matter and junction (Fig. 3B, C). Double-labeling experiments conﬁrmed that TRPC6 was expressed in NeuN-positive neurons (Fig. 3B, inset), including glutamatergic (Fig. 3E–G) and GABAergic neurons (Fig. 3H–J), and was also expressed in GFAP-positive astrocytes (Fig. 3D).FIGURE 3.