Abstract
Synaptic structural and functional damage is a typical pathological feature of Alzheimer's disease (AD). Normal axonal mitochondrial function and transportation are vital to synaptic function and plasticity because they are necessary for maintaining cellular energy supply and regulating calcium and redox signalling as well as synaptic transmission and vesicle release. Amyloid-β (Aβ) accumulation is another pathological hallmark of AD that mediates synaptic loss and dysfunction by targeting mitochondria. Therefore, it is important to develop strategies to protect against synaptic mitochondrial damage induced by Aβ. The present study examined the beneficial effects of berberine, a natural isoquinoline alkaloid extracted from the traditional medicinal plant Coptis chinensis, on Aβ-induced mitochondrial and synaptic damage in primary cultured hippocampal neurons. We demonstrate that berberine alleviates axonal mitochondrial abnormalities by preserving the mitochondrial membrane potential and preventing decreases in ATP, increasing axonal mitochondrial density and length, and improving mitochondrial motility and trafficking in cultured hippocampal neurons. Although the underlying protective mechanism remains to be elucidated, the data suggest that the effects of berberine were in part related to its potent antioxidant activity. These findings highlight the neuroprotective and specifically mitoprotective effects of berberine treatment under conditions of Aβ enrichment.
Highlights
Synaptic dysfunction is an early event in the pathogenesis of Alzheimer’s disease (AD), and memory and cognitive loss is more strongly correlated with synaptic dysfunction than with the development of senile plaques, neurofibrillary tangles, or gliosis [1,2,3]
Neurons treated with oligomeric Aβ1-42 showed a significant, dose-dependent decline in viability, while treatment with berberine at concentrations up to 1.5 μM had no effect on cell viability (Figures 1(a) and 1(b))
Berberine is a natural isoquinoline alkaloid that has an array of neuroprotective properties; yet a majority of researches has focused on its beneficial effects on neurodegenerative diseases based on its antioxidant activity [23]
Summary
Synaptic dysfunction is an early event in the pathogenesis of Alzheimer’s disease (AD), and memory and cognitive loss is more strongly correlated with synaptic dysfunction than with the development of senile plaques, neurofibrillary tangles, or gliosis [1,2,3]. Synapses are the basic functional unit of signal transduction in the central nervous system, forming connections and transmitting electrical and chemical signals between neurons. Synapses are sites of high energy demand [4]. Adequate mitochondrial function is critical to meeting the high energy requirements of the synapse. Synaptic mitochondria are synthesized in neuronal soma, transported to axons and dendrites, and distributed among synapses to support synaptic function and modulate calcium homeostasis [5, 6]. Recent studies indicate that the appropriate intracellular distribution and trafficking of mitochondria are essential for normal neuronal functions
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