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Shibaguchi, Hirotomo; Takemura, Keiko; Kan, Shukei; Kataoka, Yasufumi; Kaibara, Muneshige; Saito, Naoaki; Taniyama, Kohtaro

doi:10.1023/a:1007022428041

Cited by 17 publications

(5 citation statements)

References 22 publications

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“…It is uncertain how this interaction works, Gordon et al propose a role for synaptophysin during SV recycling, retrieving synaptobrevin during SV endocytosis [59]. The decrease in synaptophysin points to a decrease in synaptic density, its expression has been linked both to DA release as well as to motor performance in a mouse model for PD [60, 61]. We postulate that a higher α-SYN load at the level of the synapse induces presynaptic alterations, resulting in aggravated motor dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease

Torre-Muruzabal

Devoght

Haute

et al. 2019

acta neuropathol commun

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Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson’s disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD.

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Section: Discussionmentioning

confidence: 99%

Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease

Torre-Muruzabal

Devoght

Haute

et al. 2019

acta neuropathol commun

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“…Early studies in Xenopus reconstitution systems suggested a central role for synaptophysin in neurotransmitter release using either its overexpression or injection of antisense or antibodies to perturb its function [5][6][7][8]. However, when synaptophysin knockout mice were generated, they were viable and had no obvious defects in neurotransmitter release [9,10].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine phosphorylation of synaptophysin in synaptic vesicle recycling

Evans

Cousin

2005

Biochemical Society Transactions

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The integral SV (synaptic vesicle) protein synaptophysin was one of the first nerve terminal proteins identified. However its role, if any, in the SV life cycle remains undetermined. One of the most prominent features of synaptophysin is that its cytoplasmic C-terminus largely consists of pentapeptide repeats initiated by a tyrosine residue. Synaptophysin is heavily phosphorylated by tyrosine kinases in the nerve terminal, suggesting that this phosphorylation is central to its function. This review will cover the evidence for tyrosine phosphorylation of synaptophysin and how this phosphorylation may control its function in the SV life cycle.

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“…PSD-95 interacts with various binding partners, such as associated synaptic proteins, ion channels, and cytoskeletal elements, to form a complex network that stabilizes and regulates synaptic function, transmission and formation and maintenance of dendritic spines, receptor tra cking, and synaptic signaling and plasticity mechanisms [45][46][47][48] . Synaptophysin is involved in synaptic plasticity 49 , and in synaptic vesicle exocytosis 50,51 . It is an integral component of the synaptic vesicle membrane and interacts with other proteins to regulate vesicle fusion with the presynaptic membrane, thereby facilitating the release of neurotransmitters into the synapse [52][53][54] .…”

Section: Discussionmentioning

confidence: 99%

Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract

Lerer

Shahar

Botvinnik

et al. 2023

Preprint

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Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or “full spectrum” (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 minutes. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins are indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas studied for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis – Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.

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Cited by 17 publications

References 22 publications

Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease

Chronic nigral neuromodulation aggravates behavioral deficits and synaptic changes in an α-synuclein based rat model for Parkinson’s disease

Tyrosine phosphorylation of synaptophysin in synaptic vesicle recycling

Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract

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