Opposite modulation of time course of quantal release in two parts of the same synapse by reactive oxygen species

Tsentsevitsky, A. N.; Nikolsky, E. E.; Giniatullin, Rashid; Bukharaeva, É. A.

doi:10.1016/j.neuroscience.2011.05.033

Cited by 16 publications

(13 citation statements)

References 40 publications

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“…Thus, it was shown in our study that spontaneous release was compromised much more strongly than evoked secretion underlying Ca 2+ -dependent EPPs. However, in the frame of oxidative mechanism of neurodegeneration in ALS this is a very consistent observation since spontaneous release was preferentially inhibited by the oxidative challenge (Giniatullin et al, 2006; Tsentsevitsky et al, 2011). Moreover, unlike earlier hypothesis, current evidence suggests the possibility of differential regulation of spontaneous and evoked neurotransmitter release (Ramirez and Kavalali, 2011).…”

Section: Discussionmentioning

confidence: 72%

Gender-Specific Mechanism of Synaptic Impairment and Its Prevention by GCSF in a Mouse Model of ALS

Naumenko

Pollari

Kurronen

et al. 2011

Front. Cell. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motoneurons which progresses differentially in males and females for unknown reason. Here we measured gender differences in pre- and post-synaptic parameters of the neuromuscular transmission in a mutant G93A-SOD1 mouse model of ALS. Using intracellular microelectrode technique we recorded miniature and evoked end-plate potentials (MEPPs and EPPs) in the diaphragm muscle of G93A-SOD1 mice at early symptomatic stage. While no evident alterations in the amplitude of MEPPs was observed in male or female G93A-SOD1 mice, G93A-SOD1 mice displayed dramatically reduced probability of spontaneous acetylcholine release. In contrast, the EPPs evoked by single nerve stimulation had unchanged amplitude and quantal content. In males, but not females, this was accompanied by reduced readily releasable transmitter pool. Transmitter release in both sexes was sensitive to the inhibitory action of reactive oxygen species (ROS), but the production of ROS was increased in the spinal cords of male but not female G93A-SOD1 mice. Treatment with granulocyte colony stimulating factor (GCSF), which we previously found to be beneficial in males, attenuated the increased ROS production indicating involvement of the antioxidant mechanisms and improved ALS-induced synaptic dysfunctions only in males being ineffective in females. Consistent with our findings at synaptic level, GCSF did not change the survival rate or motor performance of female ALS mice. In summary, neuromuscular transmission in ALS mice is impaired at early symptomatic stage when a dramatic presynaptic decline of spontaneous release occurs. Beneficial effects of GCSF treatment on survival in males may be explained by GCSF-improved presynaptic functions in male G93A-SOD1 mice. Development of efficient treatment strategies for ALS may need to be directed in a gender-specific manner.

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Section: Discussionmentioning

confidence: 72%

Gender-Specific Mechanism of Synaptic Impairment and Its Prevention by GCSF in a Mouse Model of ALS

Naumenko

Pollari

Kurronen

et al. 2011

Front. Cell. Neurosci.

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“…For example, elevated synaptic ROS levels have been shown to decrease glutamate reuptake after release in rat brain synaptosomes [11]. Transient application of hydrogen peroxide and Fe 2+ to frog and mouse NMJs inhibits both spontaneous and evoked release [12]. These inhibitory effects of exogenous ROS on spontaneous release closely resemble alterations in neurotransmission seen in mouse models of amyotrophic lateral sclerosis that overexpress mutant variants of human SOD1 [5].…”

Section: Introductionmentioning

confidence: 91%

The Lack of CuZnSOD Leads to Impaired Neurotransmitter Release, Neuromuscular Junction Destabilization and Reduced Muscle Strength in Mice

et al. 2014

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Elevated reactive oxygen species (ROS) production and ROS-dependent protein damage is a common observation in the pathogenesis of many muscle wasting disorders, including sarcopenia. However, the contribution of elevated ROS levels to –a breakdown in neuromuscular communication and muscle atrophy remains unknown. In this study, we examined a copper zinc superoxide dismutase [CuZnSOD (Sod1)] knockout mouse (Sod1 −/−), a mouse model of elevated oxidative stress that exhibits accelerated loss of muscle mass, which recapitulates many phenotypes of sarcopenia as early as 5 months of age. We found that young adult Sod1 −/− mice display a considerable reduction in hind limb skeletal muscle mass and strength when compared to age-matched wild-type mice. These changes are accompanied by gross alterations in neuromuscular junction (NMJ) morphology, including reduced occupancy of the motor endplates by axons, terminal sprouting and axon thinning and irregular swelling. Surprisingly however, the average density of acetylcholine receptors in endplates is preserved. Using in vivo electromyography and ex vivo electrophysiological studies of hind limb muscles in Sod1 −/− mice, we found that motor axons innervating the extensor digitorum longus (EDL) and gastrocnemius muscles release fewer synaptic vesicles upon nerve stimulation. Recordings from individually identified EDL NMJs show that reductions in neurotransmitter release are apparent in the Sod1 −/− mice even when endplates are close to fully innervated. However, electrophysiological properties, such as input resistance, resting membrane potential and spontaneous neurotransmitter release kinetics (but not frequency) are similar between EDL muscles of Sod1 −/− and wild-type mice. Administration of the potassium channel blocker 3,4-diaminopyridine, which broadens the presynaptic action potential, improves both neurotransmitter release and muscle strength. Together, these results suggest that ROS-associated motor nerve terminal dysfunction is a contributor to the observed muscle changes in Sod1 −/− mice.

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“…For example, exposure of frog NMJs to H 2 O 2 revealed their capability to directly regulate synaptic release probabilities. While synaptic strength remained unchanged, the authors observed altered quantal release synchronicity when comparing proximal vs. distal parts of the NMJ, suggesting a modulatory role for ROS or redox state with subsynaptic resolution . In a follow‐up study the same group identified SNAP‐25, a component of the SNARE complex and regulator of synaptic vesicle fusion, as a direct ROS target, whose oxidation by H 2 O 2 mediated downregulation of release synchronicity .…”

Section: Synaptic Transmission and Plasticitymentioning

confidence: 96%

“…(1) Presynaptic ROS , derived from mitochondria or NADPH oxidase activity regulates vesicle release via oxidation of SNAP ‐25 . ROS regulate release probabilities with subsynaptic terminal resolution . (2) Increases in ROS lead to activation of JNK and AP ‐1, which promote expression of antioxidant encoding genes and others required for autophagy .…”

Section: Synaptic Transmission and Plasticitymentioning

confidence: 99%

Regulation of neuronal development and function by ROS

et al. 2018

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Reactive oxygen species (ROS) have long been studied as destructive agents in the context of nervous system ageing, disease and degeneration. Their roles as signalling molecules under normal physiological conditions is less well understood. Recent studies have provided ample evidence of ROS‐regulating neuronal development and function, from the establishment of neuronal polarity to growth cone pathfinding; from the regulation of connectivity and synaptic transmission to the tuning of neuronal networks. Appreciation of the varied processes that are subject to regulation by ROS might help us understand how changes in ROS metabolism and buffering could progressively impact on neuronal networks with age and disease.

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Opposite modulation of time course of quantal release in two parts of the same synapse by reactive oxygen species

Cited by 16 publications

References 40 publications

Gender-Specific Mechanism of Synaptic Impairment and Its Prevention by GCSF in a Mouse Model of ALS

Gender-Specific Mechanism of Synaptic Impairment and Its Prevention by GCSF in a Mouse Model of ALS

The Lack of CuZnSOD Leads to Impaired Neurotransmitter Release, Neuromuscular Junction Destabilization and Reduced Muscle Strength in Mice

Regulation of neuronal development and function by ROS

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