Synaptophysin: leading actor or walk‐on role in synaptic vesicle exocytosis?

Valtorta, Flavia; Pennuto, Maria; Bonanomi, Dario; Benfenati, Fabio

doi:10.1002/bies.20012

Cited by 299 publications

(217 citation statements)

References 67 publications

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“…PSD95 is a scaffolding protein involved in glutamate receptor clustering and postsynaptic intracellular signaling (Elias & Nicoll, 2007), and synaptophysin is an integral membrane vesicular synaptic glycoprotein implicated in vesicle biogenesis and recycling (Valtorta, Pennuto, Bonanomi, & Benfenati, 2004). WB analyses revealed that in both trained and untrained animals the total amount of PSD95 protein was significantly reduced in the hippocampus of IUGR animals compared to the control and ischemic groups.…”

Section: Resultsmentioning

confidence: 99%

“…Presynaptic machinery is also affected by utero‐placental insufficiency and is shown by reduced protein levels of synaptophysin in the hippocampus of naive IUGR rats and the recovery of normal levels after training. Synaptophysin is a presynaptic protein involved in synaptic vesicle biogenesis and trafficking that increases in parallel with the formation of synapses and is frequently used as an indicator of total synaptic vesicles pools (Valtorta et al., 2004). It is known that positive stimuli such as physical exercise and environmental enrichment increase synaptic proteins expression and normalize interneuron development, and are associated with improved synaptic plasticity and cognitive function (Abel & Rissman, 2013; Chen, Chen, Lei, & Wang, 1998; Chen et al., 2006; Hu, Ying, Gomez‐Pinilla, & Frautschy, 2009; Komitova et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

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Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

et al. 2017

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“…For this purpose, the protein levels of the postsynaptic density protein 95 (PSD95), synaptophysin, and vesicle-associated membrane protein 2 (VAMP2), which are crucial for neurotransmission and synaptic plasticity [19] , were detected by Western blot. As expected, compared with the controls, the expression of PSD95, synaptophysin, and VAMP2 was decreased to 66%±3.7%, 46%±4.7%, and 50%±4.1%, respectively, after exposure to STZ for 8 h. However, LX2343 dose-dependently abolished the STZ-induced reduction in the expression of these proteins, thereby implying the potential protection of this compound against synapse integrity ( Figure 1G, 1H).…”

Section: Lx2343 Protected Neurons From Apoptosis By Ameliorating Os Amentioning

confidence: 99%

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

et al. 2017

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alzheimer's disease (aD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in aD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of aD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin (STZ) was used to induce OS in neuronal cells in vitro and in aD model rats that were made by intracerebroventricular injection of STZ (3 mg/kg, bilaterally), and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 (5-20 μmol/L) significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase aTP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3β inhibitor with IC 50 of 1.84±0.07 μmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 (7, 21 mg·kg -1 ·d -1 , ip, for 5 weeks) efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of aD.

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“…To label presynaptic synapses (output synapses), we used a synaptophysin:GFP fusion protein. Synaptophysin:GFP was the first synaptic vesicle protein to be cloned and has been extensively used to study the distribution and density of presynaptic sites in neurons both in vitro and in vivo (17)(18)(19)(20)(21)(22).We labeled progenitors for GC neurons with these genetic markers to visualize their synapse development, and observed that in adult-generated neurons, PSD-95:GFP-positive clusters (PSD ϩ C) developed initially at high density in the proximal 15% of the unbranched apical dendrite. We therefore defined the proximal 15% of the unbranched apical dendrite as the proximal domain.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Sequential development of synapses in dendritic domains during adult neurogenesis

Kelsch

Lin²,

Lois³

2008

Proc. Natl. Acad. Sci. U.S.A.

122

178

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During the process of integration into brain circuits, new neurons develop both input and output synapses with their appropriate targets. The vast majority of neurons in the mammalian brain are generated before birth and integrate into immature circuits while these are being assembled. In contrast, adult-generated neurons face an additional challenge as they integrate into a mature, fully functional circuit. Here, we examined how synapses of a single neuronal type, the granule cell in the olfactory bulb, develop during their integration into the immature circuit of the newborn and the fully mature circuit of the adult rat. We used a genetic method to label pre and postsynaptic sites in granule neurons and observed a stereotypical development of synapses in specific dendritic domains. In adult-generated neurons, synapses appeared sequentially in different dendritic domains with glutamatergic input synapses that developed first at the proximal dendritic domain, followed several days later by the development of inputoutput synapses in the distal domain and additional input synapses in the basal domain. In contrast, for neurons generated in neonatal animals, input and input-output synapses appeared simultaneously in the proximal and distal domains, respectively, followed by the later appearance of input synapses to the basal domain. The sequential formation of synapses in adult-born neurons, with input synapses appearing before output synapses, may represent a cellular mechanism to minimize the disruption caused by the integration of new neurons into a mature circuit in the adult brain.bulb ͉ dendrite I ntegration of new neurons continues throughout life in the adult mammalian olfactory bulb (OB) (1, 2). During the process of integration into brain circuits, new neurons develop both input and output synapses with their appropriate targets. Whereas the majority of neurons in the olfactory bulb integrate into an immature circuit while it is being assembled, neurons generated in adulthood face an additional challenge as they integrate into a mature, fully functional circuit. In particular, the formation of synapses by a new neuron in a functioning circuit may interfere with circuit operation and, thus, it could result in maladaptive behaviors. Additionally, it is still not known whether new neurons integrating into the neonatal and adult olfactory system have the same or different functions in the circuit and, therefore, adult-and neonatal-generated neurons could employ different modes of integration. To compare how new neurons are added to neonatal and adult circuits, we examined the pattern of synapse development of a single neuronal type, the granule cell (GC) in the olfactory bulb, during its integration into the immature circuit of the newborn and the mature circuit of the adult rat.The majority of neurons added to the OB of adult rats are GC neurons. GCs are axonless inhibitory interneurons that have both a basal dendrite and an apical dendrite (Fig. 1A). The apical dendrite can be divided into an unbranched segm...

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Synaptophysin: leading actor or walk‐on role in synaptic vesicle exocytosis?

Cited by 299 publications

References 67 publications

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

Sequential development of synapses in dendritic domains during adult neurogenesis

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