Sigma 1 receptor activation regulates brain-derived neurotrophic factor through NR2A-CaMKIV-TORC1 pathway to rescue the impairment of learning and memory induced by brain ischaemia/reperfusion

Abstract

Sig-1R activation showed an attenuation in the ischaemia/reperfusion model and the activation of Sig-1R increased the expression of BDNF, possibly through the NR2A-CaMKIV-TORC1 pathway, and Sig-1R agonists might function as neuroprotectant agents in vascular dementia.

Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder

“…In the present study, after the administration of Sig-1R agonist PRE-084, the anxiety-like behaviors and cognitive impairments were significantly reversed, indicating therapeutic benefits of activating the Sig-1R pathway. A large number of studies have shown that Sig-1R activation yields a neuroprotective effect in a variety of diseases, such as ischemia/reperfusion, Alzheimer's disease, and pain [12,13,35,36]. However, Yin et al reported that Sig-1R deficiency reduced ß-amyloid-induced hippocampal neuronal cell death and cognitive deficits, contrary to the mainstream results [37].…”

“…Not only is Sig-1R agonist regarded as one of the most efficient neuroprotective drugs, a body of evidence also exists of its beneficial effects in many disorders caused by disturbances of intercellular signaling pathways, particularly those associated with neurotrophic factors [11][12][13]. It is suggested that there is a direct relationship between Sig-1R agonists, Sig-1Rs and MAPKs and their possible roles in Sig-1R-mediated neuroprotection.…”

“…With this respect, neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), have emerged as important downstream mediators of the Sigma receptor signaling pathway [13,18]. BDNF/TrkB pathway plays a key role in activity-dependent synaptic plasticity and the formation of fear memories [19,20].…”

Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice

“…The Morris water maze (MWM) test was performed after the novel object recognition test as in our previous report [13]. The MWM consisted of a circular pool (100 cm in diameter and 50 cm in height) that was filled with water (25±1 ºC and 30 cm in depth).…”

Hypothermia-induced ischemic tolerance is associated with Drp1 inhibition in cerebral ischemia-reperfusion injury of mice

“…This test was conducted as previously described (Le et al, 2015;Yamada et al, 2011;Xu et al, 2015) with minor modifications. Briefly, each mouse was first habituated to the test arena (W 25 Â L 35Â H 40 cm) for 10 min/day for 3 days.…”