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However, the following issues need to be addressed in future studies: (1) the causal relationship among augmented hippocampal CRHR1 signaling, dendritic remodeling and stress-evoked memory loss; (2) the potential interactions between CRH and glucocorticoids (and other stress mediators) in modulating the above-mentioned effects; (3) the mechanisms underlying the relatively rapid recovery of chronic stress-induced alterations ((Conrad et al., 1999; Luine et al., 1994; McEwen, 2001), but (Elizalde et al., 2008)) and the spatiotemporal dynamics of CRH and CRHR1 during and after chronic stress exposure; (4) the differential effects of several factors such as the intensity and controllability of the chronic stress (chronic, predictable stress may facilitate spatial memory (Parihar et al., 2011)) and gender/sex hormones (McLaughlin et al., 2005) that may influence the cognitive performance under stress.
However, several issues remain to be addressed in future studies. First, it would be interesting to test the causal relationship among augmented hippocampal CRHR1 signaling, dendritic remodeling and stress-evoked memory loss. Second, more studies are needed to characterize the potential interactions between CRH and glucocorticoids (and other stress mediators) in modulating the above-mentioned effects. Another interesting question to be answered is the spatiotemporal dynamics of CRH and CRHR1 during and after chronic stress exposure. Fourth, the mechanisms underlying the relatively rapid recovery of chronic stress-induced alterations (Conrad et al., 1999; Luine et al., 1994; McEwen, 2001) need to be investigated, though long-lasting changes induced by chronic stress have also been reported (Elizalde et al., 2008). Additionally, the differential effects of several factors, such as the intensity and controllability of the chronic stress (chronic predictable stress may facilitate spatial memory (Parihar et al., 2011)) and gender/sex hormones (McLaughlin et al., 2005) that may influence the cognitive performance under stress, should be considered.
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