Expression Pattern of T-Type Ca2+ Channels in Cerebellar Purkinje Cells after VEGF Treatment.

Jonas Tjaden,Matthias Vorgerd,Julian Gehmeyr,Annika Eickhoff,Carsten Theiss,Veronika Matschke,Sarah Stahlke,Verena Theis

doi:10.3390/cells10092277

Jonas Tjaden, Matthias Vorgerd + Show 6 more

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https://doi.org/10.3390/cells10092277

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T-type Ca2+ channels, generating low threshold calcium influx in neurons, play a crucial role in the function of neuronal networks and their plasticity. To further investigate their role in the complex field of research in plasticity of neurons on a molecular level, this study aimed to analyse the impact of the vascular endothelial growth factor (VEGF) on these channels. VEGF, known as a player in vasculogenesis, also shows potent influence in the central nervous system, where it elicits neuronal growth. To investigate the influence of VEGF on the three T-type Ca2+ channel isoforms, Cav3.1 (encoded by Cacna1g), Cav3.2 (encoded by Cacna1h), and Cav3.3 (encoded by Cacna1i), lasermicrodissection of in vivo-grown Purkinje cells (PCs) was performed, gene expression was analysed via qPCR and compared to in vitro-grown PCs. We investigated the VEGF receptor composition of in vivo- and in vitro-grown PCs and underlined the importance of VEGF receptor 2 for PCs. Furthermore, we performed immunostaining of T-type Ca2+ channels with in vivo- and in vitro-grown PCs and showed the distribution of T-type Ca2+ channel expression during PC development. Overall, our findings provide the first evidence that the mRNA expression of Cav3.1, Cav3.2, and Cav3.3 increases due to VEGF stimulation, which indicates an impact of VEGF on neuronal plasticity.

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The vascular endothelial growth factor (VEGF) was first discovered in 1983, where it was responsible for the massive ascites of peritoneal tumors by increasing vascular permeability [1]
To investigate the influence of VEGF on the three T-type Ca2+ channel isoforms, Cav3.1, Cav3.2, and Cav3.3, lasermicrodissection of in vivo-grown Purkinje cells (PCs) was performed, gene expression was analysed via qPCR and compared to in vitro-grown PCs
At stage p9, the cerebellar cortex consists of four layers: the external granular cell layer, the molecular layer (ML), the PC layer (PCL), and the internal granular cell layer

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Introduction

The vascular endothelial growth factor (VEGF) was first discovered in 1983, where it was responsible for the massive ascites of peritoneal tumors by increasing vascular permeability [1]. This, in turn, is the cellular and molecular equivalent of memorization and learning [13] It is not fully understood which extra- and intracellular mechanisms contribute to synaptic plasticity, and there are many different pathways considered to influence this reorganisation [14,15]. Recent studies took the barely known low-voltage-gated T-type Ca2+ channels into account to explain synaptic plasticity in PCs [22,23,24,25,26] These T-type Ca2+ channels can be classified into three subtypes, namely, Cav3.1 (encoded by Cacna1g), Cav3.2 (encoded by Cacna1h), and Cav3.3 (encoded by Cacna1i), and their expression in PCs was proven lately [21,27]. To extend the knowledge of the effect of VEGF, we wanted to examine its role in neuronal functioning and synaptic plasticity and analysed the expression of Cacna1g, Cacna1h, and Cacna1i after VEGF treatment

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