Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid protein (Aβ) and extensive neuronal cell death. Apoptosis plays a crucial role in loss of neurons in AD. Neuregulin1 (NRG1) has been found to protect neurons from oxygen glucose deprivation induced apoptosis and hypoxia ischemia induced apoptosis. However, the relationship between NRG1 and apoptosis related protein expression in AD and its mechanism remain uncertain. The present study explores the effects of NRG1 on Aβ-induced apoptosis in AD. In this study, extracellular domain of NRG1beta1 (NRG1β1-ECD) promoted the expression of p-ErbB4 receptor, p-Akt and increased the level of Bcl-2 both in APP/PS1 transgenic mice and in vitro. In primary culture of neurons, the level of Bcl-2 protein decreased significantly after Aβ treatment. These changes were inhibited by pretreatment of neurons with NRG1β1-ECD. A specific inhibitor of PI3-kinase/Akt pathway, wortmannin, significantly abrogated the effects of NRG1β1-ECD on p-Akt and Bcl-2 levels. Furthermore, the expression of PI3-kinase/Akt by NRG1β1-ECD was ErbB4-dependent. Our data demonstrated that NRG1β1-ECD might serve as an obvious neuroprotection in AD, and the possible protective mechanism occurs most likely via ErbB4-dependent activation of PI3-kinase/Akt pathway.
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Article Synopsis
- Top-down attention, essential for meaningful behavior, is linked to the synchrony between the hippocampus and prefrontal cortex, but its regulatory mechanisms are not well understood.
- Research shows that this synchrony and attention levels drop in mutant mice lacking ErbB4, a receptor involved in brain signaling.
- Disrupting ErbB4 activity affects GABA levels, impairing hippocampal-prefrontal synchrony and attention, highlighting the significance of ErbB4 in controlling attention and its potential connection to disorders like schizophrenia and major depression.*
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