Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory synapses

Abstract

Relatively mild ischemic episode can initiate a chain of events resulting in delayed cell death and significant lesions in the affected brain regions. We studied early synaptic modifications after brief ischemia modeled in rats by transient vessels' occlusion in vivo or oxygen-glucose deprivation in vitro and resulting in delayed death of hippocampal CA1 pyramidal cells. Electron microscopic analysis of excitatory spine synapses in CA1 stratum radiatum revealed a rapid increase of the postsynaptic density (PSD) thickness and length, as well as formation of concave synapses with perforated PSD during the first 24 h after ischemic episode, followed at the long term by degeneration of 80% of synaptic contacts. In presynaptic terminals, ischemia induced a depletion of synaptic vesicles and changes in their spatial arrangement: they became more distant from active zones and had larger intervesicle spacing compared to controls. These rapid structural synaptic changes could be implicated in the mechanisms of cell death or adaptive plasticity. Comparison of the in vivo and in vitro model systems used in the study demonstrated a general similarity of these early morphological changes, confirming the validity of the in vitro model for studying synaptic structural plasticity.

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

“…In mammals, this process takes place in the CA1 region of the hippocampus, and the underlying cellular mechanism is a form of synaptic plasticity known as long‐term potentiation or LTP (Vann & Albasser, 2011), that requires Ca +2 signaling, gene expression changes and protein synthesis (Morgado‐Bernal, 2011). The neuropathological bases of learning and memory alterations in IUGR babies are not clear, but there is consensus that within the brain the hippocampus is one of the areas most susceptible to IUGR and hypoxic damage (Fung et al., 2012; Lodygensky et al., 2008; Mallard et al., 2000), which particularly affects CA1 pyramidal neurons in the hippocampus (Kovalenko et al., 2006; Lister et al., 2005). In this study, the ischemic and IUGR CMO groups presented a reduction in CA1 neuronal number, mild gliosis and paradoxical changes in PSD95 and synaptophysin expression.…”

Selective Vulnerability of Synaptic Signaling and Metabolism to Nitrosative Stress

“…Even in the animal models of MS, which are primarily associated with demyelination, loss of functional synapses was found both immediately after the onset of neurological symptoms and in remission (48,175). Robust changes in the number of synapses are commonly seen in stroke, in the peri-infarct regions, where the neuronal viability is largely preserved (3,36,126,148,194). Although the loss of synapses in ischemia can be driven by death of local and distant neuronal cells, several studies found that the ischemia-and hypoxia-induced degeneration of axonal projections and dendritic trees can occur independently of the loss of cell bodies (3,11,126).…”

Neuroprotection in Animal Models of Global Cerebral Ischemia

“…Thus, a permanent deafferentation of pyramidal neurons at cortical layer V after the extensive reduction of pyramidal neuron population of the CA1 subfield of the Ammon's horn as expected to occur after global ischemia , may lead to changes in neuronal activity, which may in turn affect the cytoarchitectural characteristics of pyramidal prefrontal cortex neurons (García-Chávez et al, 2008;Wellman & Sengelaub, 1991). These dendritic restructuring (Neigh el al., 2004;Ruan el al., 2006) and reactive synaptogenesis (Briones et al, 2005;Crepel et al, 2003;Jourdain et al, 2002, Kovalenko et al, 2006 among other phenomena including the activation of a variety of potential growth-promoting processes (Arvidsson et al, 2001;Gobbo & O´Mara, 2004;Schmidt-Kastner et al, 2001), that occur in neurons surviving to the ischemic insult in vulnerable brain structures, seem to be a part of mechanisms of adaptive changes, probably accounting for neuronal conditions favoring synaptic plasticity and functional recovery. In fact, a long-term progressive continuous plastic reorganization of the dendritic tree and dendritic spines, initially altered by acute global cerebral ischemia, has been shown to occur in pyramidal neurons at layers 3 and 5 of the sensorymotor cortex of the rat (Akulinin et al, 1997(Akulinin et al, , 1998(Akulinin et al, , 2004.…”

“…Different parameters of the glial reaction elicited by global cerebral ischemia have been used as indexes of brain damage or neuroprotection de Yebra et al, 2006;Duan et al, 2011;Korzhevskii et al, 2005;Piao et al, 2002;Soltys et al, 2003). Neuronal cytoarchitecture and fine structure parameters of synaptic connectivity have also been used for histopathological assessment after brain damage and neuroprotection (Briones et al, 2006;García-Chávez et al, 2008;González-Burgos et al, 2007;Johansson & Belichenko, 2002;Kovalenko et al, 2006, Moralí et al, 2011aNikonenko et al, 2009;Ruan et al, 2006).…”