Remodeling of synapses in the CA1 area of the hippocampus after transient global ischemia

Ruan, Yiwen; Han, Xinjia; Shi, Zhongshan; Lei, Zhigang; Xu, Zao C.

doi:10.1016/j.neuroscience.2012.05.035

Cited by 31 publications

(26 citation statements)

References 59 publications

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“…One of the most conspicuous features observed in degenerating terminal synaptic boutons and contacting dendrites was the accumulation of autophagic vacuoles, as reported in other forms of neuronal injury (95). Autophagic vacuoles were also occasionally seen in WT dendrites, presumably reflecting a postnatal remodeling of neural processes.…”

Section: Loss Of Afferent Synapses On Spinal Cord Mns In Smn$7 Micementioning

confidence: 62%

Mechanisms Involved in Spinal Cord Central Synapse Loss in a Mouse Model of Spinal Muscular Atrophy

Tarabal¹,

Caraballo-Miralles

Cardona-Rossinyol

et al. 2014

J Neuropathol Exp Neurol

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Motoneuron (MN) cell death is the histopathologic hallmark of spinal muscular atrophy (SMA), although MN loss seems to be a late event. Conversely, disruption of afferent synapses on MNs has been shown to occur early in SMA. Using a mouse model of severe SMA (SMNΔ7), we examined the mechanisms involved in impairment of central synapses. We found that MNs underwent progressive degeneration in the course of SMA, with MN loss still occurring at late stages. Loss of afferent inputs to SMA MNs was detected at embryonic stages, long before MN death. Reactive microgliosis and astrogliosis were present in the spinal cord of diseased animals after the onset of MN loss. Ultrastructural observations indicate that dendrites and microglia phagocytose adjacent degenerating presynaptic terminals. Neuronal nitric oxide synthase was upregulated in SMNΔ7 MNs, and there was an increase in phosphorylated myosin light chain expression in synaptic afferents on MNs; these observations implicate nitric oxide in MN deafferentation and suggest that the RhoA/ROCK pathway is activated. Together, our observations suggest that the earliest change occurring in SMNΔ7 mice is the loss of excitatory glutamatergic synaptic inputs to MNs; reduced excitability may enhance their vulnerability to degeneration and death.

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Section: Loss Of Afferent Synapses On Spinal Cord Mns In Smn$7 Micementioning

confidence: 62%

Mechanisms Involved in Spinal Cord Central Synapse Loss in a Mouse Model of Spinal Muscular Atrophy

Tarabal¹,

Caraballo-Miralles

Cardona-Rossinyol

et al. 2014

J Neuropathol Exp Neurol

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“…Brain ischemia triggers complex cellular mechanisms that impair synaptic functions through the breakdown of cellular and structural features, mediated by various excitotoxic signals [35,37,38]. It is well known that the CA1 area of hippocampus is particularly vulnerable to ischemic insult [39,40].…”

Section: Discussionmentioning

confidence: 99%

Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures

Jung

Suh

Lee

2012

Korean J Physiol Pharmacol

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Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.

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“…In addition to the human disorders mentioned above, the impact of autophagy on synaptic pathology has also been addressed in other laboratory models of neurological diseases including ischemia [89] , electroconvulsive seizures [90] , and neurotoxicity [91] .…”

Section: Oxidative Stress Burdenmentioning

confidence: 99%

Autophagy in synaptic development, function, and pathology

et al. 2015

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In the nervous system, neurons contact each other to form neuronal circuits and drive behavior, relying heavily on synaptic connections. The proper development and growth of synapses allows functional transmission of electrical information between neurons or between neurons and muscle fi bers. Defects in synapse-formation or development lead to many diseases. Autophagy, a major determinant of protein turnover, is an essential process that takes place in developing synapses. During the induction of autophagy, proteins and cytoplasmic components are encapsulated in autophagosomes, which fuse with lysosomes to form autolysosomes. The cargoes are subsequently degraded and recycled. However, aberrant autophagic activity may lead to synaptic dysfunction, which is a common pathological characteristic in several disorders. Here, we review the current understanding of autophagy in regulating synaptic development and function. In addition, autophagy-related synaptic dysfunction in human diseases is also summarized.

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Remodeling of synapses in the CA1 area of the hippocampus after transient global ischemia

Cited by 31 publications

References 59 publications

Mechanisms Involved in Spinal Cord Central Synapse Loss in a Mouse Model of Spinal Muscular Atrophy

Mechanisms Involved in Spinal Cord Central Synapse Loss in a Mouse Model of Spinal Muscular Atrophy

Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures

Autophagy in synaptic development, function, and pathology

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