A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS.

A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS. Exp Neurol. 2017 Sep 04;: Authors: Stagni F, Giacomini A, Guidi S, Emili M, Uguagliati B, Salvalai ME, Bortolotto V, Grilli M, Rimondini R, Bartesaghi R Abstract Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB). Systemic BDNF administration is impracticable because BDNF has a poor blood-brain barrier penetration. Recent screening of a chemical library has identified a flavone derivative, 7,8-dihydroxyflavone (7,8-DHF), a small-molecule that crosses the blood-brain barrier and binds with high affinity and specificity to the TrkB receptor. The therapeutic potential of TrkB agonists for neurogenesis improvement in DS has never been examined. The goal of our study was to establish whether it is possible to restore brain development in the Ts65Dn mouse model of DS by targeting the TrkB receptor with 7,...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research