miR‐206 regulates brain‐derived neurotrophic factor in Alzheimer disease model

Abstract

Our findings demonstrate a novel miRNA-dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206.

microRNA-206 in Rat Medial Prefrontal Cortex Regulates BDNF Expression and Alcohol Drinking

“…Our finding that miR-206 is able to directly repress BDNF translation is in agreement with previous studies and supports the notion that miR-mediated changes in synaptic plasticity may underlie behavioral consequences of alcohol dependence (Lee et al, 2012;Miura et al, 2012). BDNF is a potent modulator of synaptic transmission and plasticity in cortical neurons (Horch et al, 1999) and is involved in the regulation of alcohol consumption and preference in nondependent animals (McGough et al, 2004).…”

“…In the normal human or rodent brain, miR-206 is expressed at very low basal levels, but its expression is induced under disease conditions, such as in Alzheimer's disease. For instance, high expression of miR-206 was shown in brains of Alzheimer's disease transgenic mice and in the temporal cortex of Alzheimer's disease patients (Lee et al, 2012). Our findings indicate that brain alcohol exposure is an insult that also results in a persistent, region-specific induction of miR-206 expression, with clear consequences for neuronal function and behavior.…”

“…Arc physically modulates dendritic spine density (DSD) and function (Messaoudi et al, 2007;Bramham et al, 2010). Inhibiting miR-206 in vivo increased BDNF expression and subsequently increased DSD and neurogenesis in the mouse hippocampus (Lee et al, 2012).…”

Maternal immune activation alters brain microRNA expression in mouse offspring

“…microRNA (miRNA) is a well‐known epigenetic component that post‐transcriptionally regulates gene expression by binding to complementary nucleotide sequences in the 3′ untranslated region of target mRNAs 5. Altered miRNA expression has been associated with neurological disorders, including Alzheimer's disease,6 schizophrenia,7 and ASD 8, 9. Therefore, miRNAs may act as epigenetic factors in complex ASD etiologies, however, there have been substantial differences reported in miRNA expression profiles among different studies 10.…”

Progress in Alzheimer’s disease research in the last year

“…Regarding in vivo models, Lee et al [22] analyzed micro(mi)RNA-206 expression in Tg2576 transgenic mice and human AD brain samples. They demonstrated that mouse brains and the temporal cortex of human AD brains had increased levels of miR-206, which targets brainderived neurotrophic factor (BDNF) transcripts.…”