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Hyperactivation of BDNF-TrkB signaling cascades in human hypothalamic hamartoma (HH): a potential mechanism contributing to epileptogenesis.


ABSTRACT:

Aims

Although compelling evidence suggests that human hypothalamic hamartoma (HH) is intrinsically epileptogenic for gelastic seizures, the molecular mechanisms responsible for epileptogenesis within HH remain to be elucidated. The aim of this study was to test the hypothesis that hyperactivation of BDNF-TrkB signaling pathways in surgically resected HH tissue is a possible mechanism for downregulation of KCC2 expression, which in turn underlies GABA-mediated excitation within HH.

Methods

Activation of three major BDNF-TrkB signaling pathways including MAPKs, Akt, and PLCγ1 were evaluated in surgically resected HH tissue (n = 14) versus human hypothalamic control tissue (n = 8) using combined methodologies of biochemistry, molecular biology, cell biology, and electrophysiolo

SUBMITTER: Semaan S 

PROVIDER: S-EPMC6495156 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature