scholarly journals Berberine Alleviates Amyloid β-Induced Mitochondrial Dysfunction and Synaptic Loss

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Chunhui Zhao ◽  
Ping Su ◽  
Cui Lv ◽  
Limin Guo ◽  
Guoqiong Cao ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Isoquinoline Alkaloid ◽  
Synaptic Function ◽  
Protective Mechanism ◽  
Pathological Feature ◽  
Synaptic Loss ◽  
Beneficial Effects ◽  
Mitochondrial Motility ◽  
Cultured Hippocampal Neurons

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.

scholarly journals L-type Ca2+ channel–mediated Ca2+ influx adjusts neuronal mitochondrial function to physiological and pathophysiological conditions

2020 ◽  
Vol 13 (618) ◽  
pp. eaaw6923 ◽  
Author(s):  
Matej Hotka ◽  
Michal Cagalinec ◽  
Karlheinz Hilber ◽  
Livia Hool ◽  
Stefan Boehm ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Atp Synthase ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Mitochondrial Depolarization ◽  
Voltage Gated ◽  
Beneficial Effects ◽  
Reverse Mode ◽  
Cultured Hippocampal Neurons

L-type voltage-gated Ca2+ channels (LTCCs) are implicated in neurodegenerative processes and cell death. Accordingly, LTCC antagonists have been proposed to be neuroprotective, although this view is disputed, because intentional LTCC activation can also have beneficial effects. LTCC-mediated Ca2+ influx influences mitochondrial function, which plays a crucial role in the regulation of cell viability. Hence, we investigated the effect of modulating LTCC-mediated Ca2+ influx on mitochondrial function in cultured hippocampal neurons. To activate LTCCs, neuronal activity was stimulated by increasing extracellular K+ or by application of the GABAA receptor antagonist bicuculline. The activity of LTCCs was altered by application of an agonistic (Bay K8644) or an antagonistic (isradipine) dihydropyridine. Our results demonstrated that activation of LTCC-mediated Ca2+ influx affected mitochondrial function in a bimodal manner. At moderate stimulation strength, ATP synthase activity was enhanced, an effect that involved Ca2+-induced Ca2+ release from intracellular stores. In contrast, high LTCC-mediated Ca2+ loads led to a switch in ATP synthase activity to reverse-mode operation. This effect, which required nitric oxide, helped to prevent mitochondrial depolarization and sustained increases in mitochondrial Ca2+. Our findings indicate a complex role of LTCC-mediated Ca2+ influx in the tuning and maintenance of mitochondrial function. Therefore, the use of LTCC inhibitors to protect neurons from neurodegeneration should be reconsidered carefully.

Amyloid β-peptide(1–40)-mediated oxidative stress in cultured hippocampal neurons

1998 ◽  
Vol 10 (3) ◽  
pp. 181-192 ◽  
Author(s):  
Michael Y. Aksenov ◽  
Marina V. Aksenova ◽  
William R. Markesbery ◽  
D. Allan Butterfield
Keyword(s):  
Oxidative Stress ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Cultured Hippocampal Neurons

Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons

2009 ◽  
Vol 122 (4) ◽  
pp. 524-534 ◽  
Author(s):  
A. Ivanov ◽  
M. Esclapez ◽  
C. Pellegrino ◽  
T. Shirao ◽  
L. Ferhat
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Synaptic Function ◽  
Spine Plasticity ◽  
Cultured Hippocampal Neurons

scholarly journals Amyloid-β oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons

2013 ◽  
Vol 24 (16) ◽  
pp. 2494-2505 ◽  
Author(s):  
Elisa M. Ramser ◽  
Kathlyn J. Gan ◽  
Helena Decker ◽  
Emily Y. Fan ◽  
Matthew M. Suzuki ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Amyloid Β ◽  
Protein Phosphatase 1 ◽  
Organelle Transport ◽  
Calcium Dependent ◽  
Pathological Event ◽  
Cultured Hippocampal Neurons

Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AβOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3β, downstream targets of CaN, prevents BDNF transport defects induced by AβOs. We further show that AβOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AβO-induced BDNF transport disruption.

scholarly journals Direct interaction of HIV gp120 with neuronal CXCR4 and CCR5 receptors induces cofilin-actin rod pathology via a cellular prion protein- and NOX-dependent mechanism

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248309
Author(s):  
Lisa K. Smith ◽  
Isaac W. Babcock ◽  
Laurie S. Minamide ◽  
Alisa E. Shaw ◽  
James R. Bamburg ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Prion Protein ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Direct Interaction ◽  
Cellular Prion Protein ◽  
Synaptic Function ◽  
Viral Envelope ◽  
Glycoprotein Gp120

Nearly 50% of individuals with long-term HIV infection are affected by the onset of progressive HIV-associated neurocognitive disorders (HAND). HIV infiltrates the central nervous system (CNS) early during primary infection where it establishes persistent infection in microglia (resident macrophages) and astrocytes that in turn release inflammatory cytokines, small neurotoxic mediators, and viral proteins. While the molecular mechanisms underlying pathology in HAND remain poorly understood, synaptodendritic damage has emerged as a hallmark of HIV infection of the CNS. Here, we report that the HIV viral envelope glycoprotein gp120 induces the formation of aberrant, rod-shaped cofilin-actin inclusions (rods) in cultured mouse hippocampal neurons via a signaling pathway common to other neurodegenerative stimuli including oligomeric, soluble amyloid-β and proinflammatory cytokines. Previous studies showed that synaptic function is impaired preferentially in the distal proximity of rods within dendrites. Our studies demonstrate gp120 binding to either chemokine co-receptor CCR5 or CXCR4 is capable of inducing rod formation, and signaling through this pathway requires active NADPH oxidase presumably through the formation of superoxide (O2-) and the expression of cellular prion protein (PrPC). These findings link gp120-mediated oxidative stress to the generation of rods, which may underlie early synaptic dysfunction observed in HAND.

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