Changes in Mint1, a Novel Synaptic Protein, After Transient Global Ischemia in Mouse Hippocampus

Abstract

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is involved in synaptic vesicle exocytosis. Its potential effects on development of ischemic damage to neurons have not yet been evaluated. The authors examined changes in mint1 and other synaptic proteins by immunohistochemistry after transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhinal cortex to the hippocampus and in the mossy fibers linking the granule cells of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partner of mint1, was distributed uniformly throughout the hippocampus, and synaptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibers. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enhancement at 3 days. However, munc18-1 and synaptophysin 2 were substantially expressed in the same region throughout the reperfusion period. These findings suggest that mint1 participates in neuronal transmission along the excitatory pathway linking the entorhinal cortex to CA3 in the hippocampus. Because mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delayed neuronal death.

Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory synapses

“…It has been shown in many studies that SV proteins change their phosphorylation level under physiological and pathological conditions (Genoud et al, 1999;Bolay et al, 2002;Jung et al, 2004). SNAP-25, synapsin, synaptotagmins, and mint1, which are all implicated in the regulation of synaptic transmission and SV cycling, have been reported to be modified either in their expression level or their phosphorylation following transient ischemia (Nishimura et al, 2000;Ishimaru et al, 2001;Nakajima et al, 2001;Yokota et al, 2001;Bolay et al, 2002;Jung et al, 2004). Together, all these data suggest alterations of presynaptic proteins which could result in impairment of synaptic function.…”

Astrocyte‐derived lipocalin‐2 mediates hippocampal damage and cognitive deficits in experimental models of vascular dementia

“…A statistically significant drop in CBF was confirmed (Supporting Information, Figure S1). The tBCCAo rodent model specifically targeted the hippocampal CA1 neurons and was useful in establishing the possible cellular and molecular underpinnings of neuronal death by this particular condition (Nishimura et al, ; Pontarelli, Ofengeim, Zukin, & Jonas, ; Qi et al, ; Yang et al, ). Our results indicate that the tBCCAo animal model of global ischemia can be further used to study the role of LCN2 upregulation in selective hippocampal neuronal death and ensuing cognitive dysfunction.…”

Prolonged Therapeutic Hypothermia does not Adversely Impact Neuroplasticity after Global Ischemia in Rats

“…Mossy fiber plasticity, including that measured with synaptophysin labeling, occurs after global ischemia (Nishimura et al, 2000) and other injuries, such as trauma and epilepsy (Li et al, 2002). Although the exact function of synaptophysin is unknown, the protein is expressed within presynaptic membranes and is used as a marker for functional synapses (Hinz et al, 2001;Li et al, 2002).…”

“…Third, plasticity responses within the hippocampus are well documented and are strongly linked to behavioral recovery. For example, mossy fiber sprouting is elevated on the third postischemic day and remains elevated until at least 7 days (Koh et al, 1996;Nishimura et al, 2000;Schmidt-Kastner et al, 1997). Also, ischemia markedly elevates neurogenesis in the subgranular zone of the dentate gyrus (DG) (Liu et al, 1998).…”