Berberine and Alzheimer Dementia

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Berberine and Alzheimer dementia

Berberine Alleviates Amyloid β-Induced Mitochondrial Dysfunction and Synaptic Loss

 

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.  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 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.

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 [1–3]. Synapses are the basic functional unit of signal transduction in the central nervous system, forming connections and transmitting electrical and chemical signals between neurons.

Accordingly, 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 also indicate that the appropriate intracellular distribution and trafficking of mitochondria are essential for normal neuronal functions including neurotransmission, synaptic plasticity, and axonal outgrowth [7–9]. Importantly, abnormalities in mitochondrial function play an important role in AD [6].

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Amyloid β (Aβ) is an important pathogenic peptide that is associated with AD and directly disturbs mitochondrial function [10, 11]. Aβ is transported into the mitochondria via the receptor for advanced glycation end products, the translocase of the outer mitochondrial membrane, or endoplasmic reticulum-mitochondrial crosstalk [10, 12–14]. Mitochondrial Aβ accumulation impairs mitochondrial respiration, decreases ATP production and the mitochondrial membrane potential, and increases calcium influx, cytochrome c release, and oxidative stress [15, 16]. Furthermore, the interaction of Aβ with proteins such as alcohol dehydrogenase and cyclophilin D exacerbates Aβ-induced mitochondrial and neuronal stress [17–20].

Recent studies indicate that brief exposure of cultured hippocampal neurons to relatively low concentrations of Aβ is sufficient to mediate the rapid (within 10 min) and severe impairment of mitochondrial transport in the absence of apparent cell death or significant morphological changes [21]. Taken together, these studies suggest that mitochondria are a direct site for Aβ-mediated cellular perturbation and that overt mitochondrial dysfunction occurs in an Aβ-rich environment.

Berberine is a natural isoquinoline alkaloid derived from the traditional medicinal plant Coptis chinensis

that has numerous pharmacological properties including antimicrobial, antioxidant, anti-inflammatory, antidiarrheal, antidiabetic, antidyslipidemic, and antitumour activities [22, 23]. Recent studies have indicated that berberine treatment significantly improves memory and cognitive dysfunction in different animal models of AD [24, 25].

Due to its ability to cross the blood-brain barrier [26], berberine exerts beneficial neuroprotective effects against homocysteic acid, calyculin A, 6-hydroxydopamine, streptozotocin, and mercury-induced neurodegeneration as demonstrated through in vivo and in vitro studies [27–31]. Furthermore, berberine treatment inhibits Aβ25–35-induced cytotoxicity and apoptosis by suppressing the release of cytochrome C, apoptotic protein expression, and caspase activity in primary cultured hippocampal neurons [32]. Yet whether berberine has protective effects against Aβ-induced mitochondrial dysfunction and synaptic loss in neurons remains unclear. Therefore, we investigated the effects of berberine on Aβ oligomer-induced axonal mitochondrial dysfunction using an in vitro hippocampal neuron-cultured model.

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Reference article :
AbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsAbbreviationsData AvailabilityConflicts of InterestAcknowledgmentsReferencesCopyright
Research Article | Open Access
Volume 2019 |Article ID 7593608 | 11 pages | https://doi.org/10.1155/2019/7593608
Berberine Alleviates Amyloid β-Induced Mitochondrial Dysfunction and Synaptic Loss
Chunhui Zhao,1,2,3 Ping Su,1,2,3 Cui Lv,1,2,4 Limin Guo,1,2,5 Guoqiong Cao,1,2,5 Chunxia Qin,1,2,5 and Wensheng Zhang1,2,5,6
Academic Editor: Ana Lloret

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