Acute Restraint Stress Enhances Calcium Mobilization and Glutamate Exocytosis in Cerebrocortical Synaptosomes from Mice

Abstract

Acute stress is known to enhance the memory of events that are potentially threatening to the organisms. Glutamate, the most abundant excitatory neurotransmitter in the mammalian central nervous system, plays a critical role in learning and memory formation and calcium (Ca(2+)) plays an essential role in transmitter release from nerve terminals (synaptosomes). In the present study, we investigated the effects of acute restraint stress on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and glutamate release in cerebrocortical synaptosomes from mice. Acute restraint stress caused a significant increase in resting [Ca(2+)](i) and significantly enhanced the ability of the depolarizing agents K(+) and 4-aminopyridine (4-AP) to increase [Ca(2+)](i). It also brought about a significant increase in spontaneous (unstimulated) glutamate release and significantly enhanced K(+)- and 4-AP-induced Ca(2+)-dependent glutamate release. The pretreatment of synaptosomes with a combination of omega-agatoxin IVA (a P-type Ca(2+) channel blocker) and omega-conotoxin GVIA (an N-type Ca(2+) channel blocker) completely suppressed the enhancements of [Ca(2+)](i) and Ca(2+)-dependent glutamate release in acute restraint-stressed mice. These results indicate that acute restraint stress enhances K(+)- or 4-AP-induced glutamate release by increasing [Ca(2+)](i) via stimulation of Ca(2+) entry through P- and N-type Ca(2+) channels.

Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress

“…The ARS has been proposed as a model that triggers biochemical alterations in mouse brain that can be harmful to CNS function. Among these changes, an increased glutamate release (Satoh and Shimeki, 2010) and an imbalance in oxidant/antioxidant parameters were reported in rodents (Freitas et al, 2014;Kumar et al, 2010). This resulted increase in ROS production and/or inefficiency in antioxidant systems leads to oxidative stress and is implicated in several psychiatry diseases, including major depression (Bilici et al, 2001;Valko et al, 2007).…”

Towards a glutamate hypothesis of depression

“…Early in vivo microdialysis studies showed that exposure of rats to different stressors (tail-pinch, restraint, forced swim) or administration of corticosterone (the main stress hormone in rodents) rapidly and transiently induce a marked increase in the level of extracellular glutamate in different areas, including hippocampus, amygdala and prefrontal cortex (Bagley and Moghaddam, 1997; Lowy et al, 1993; Moghaddam, 1993; Venero and Borrell, 1999). Although the nature and origin of extracellular glutamate measured by microdialysis has been questioned (van der Zeyden et al, 2008), these results have been substantially confirmed by more recent works that used different methodologies measuring exocytotic release of glutamate (Cazakoff and Howland, 2010; Hascup et al, 2010; Karst et al, 2005; Musazzi et al, 2010; Reznikov et al, 2007; Satoh and Shimeki, 2010; Wang and Wang, 2009). Prefrontal cortex seems to be the area where stress induces the highest increase in glutamate release, although this effect is attenuated when stress is repeatedly applied over a short period of time (Bagley and Moghaddam, 1997; Moghaddam, 1993; Musazzi et al, 2010).…”

Erasing Synapses in Sleep: Is It Time to Be SHY?

“…Nevertheless, circadian increases in corticosterone (i.e., during the normal waking period), or after sleep deprivation may generally promote glutamatergic neurotransmission and neuronal excitability (relative to sleep) [153]. Acute increases in corticosterone (or stress) increase the frequency [154] and amplitude of mEPSCs in the hippocampus [155], strengthen glutamatergic synapses onto dopamine neurons [156], and increase glutamatergic release/calcium mobilization in cortical synaptoneurosomes [157]. Acute increases in corticosterone also promote AMPAR synaptic transmission, AMPAR trafficking and insertion into cortical and hippocampal synapses, and cortical dendritic spine turnover [158–161].…”