ISX-9 can potentiate cell proliferation and neuronal commitment in the rat dentate gyrus

Effects of Isx-9 and stress on adult hippocampal neurogenesis: Experimental considerations and future perspectives

“…However, 14 days of mild CUS also failed to induce significant changes in cell proliferation, as assessed by immunohistochemistry for the exogenous marker 5-bromo-2 0 -deoxyuridine (BrdU) [F (1,23) Despite the fact we were unable to detect an effect of stress (either restraint stress or mild CUS) on hippocampal cell proliferation and neuronal commitment, these results support our previous work showing the pro-neurogenic properties of Isx-9 in rats. 19 These findings are in agreement with previous studies, which have also failed to detect significant alterations in adult hippocampal neurogenesis following various types of stress paradigms (including acute restraint stress, acute or subchronic tailshock stress, and acute, subchronic, and chronic resident-intruder stress). 21 Together, these results further demonstrate that not all stress paradigms are associated with decreased neurogenic capacity and that multiple complex factors may modulate the neurogenic response to stress.…”

“…injections), to which all groups were submitted to, could be acting as a potential stressor on hippocampal cell proliferation and neuronal commitment. 19 This idea is in agreement with our previous study, where na€ ıve animals showed an increase in hippocampal cell proliferation and neuronal commitment when compared with vehicle-treated animals (not exposed to stress). 19 It has been shown in previous studies in rats that repeated handling can cause an increase in corticosterone levels and reduce responsiveness to both restraint stress and mild CUS.…”

“…19 This idea is in agreement with our previous study, where na€ ıve animals showed an increase in hippocampal cell proliferation and neuronal commitment when compared with vehicle-treated animals (not exposed to stress). 19 It has been shown in previous studies in rats that repeated handling can cause an increase in corticosterone levels and reduce responsiveness to both restraint stress and mild CUS. 22,23 In rats, the first exposure to restraint stress results in an elevation of glucocorticoids, but animals quickly habituate over subsequent exposures, resulting in a decrease of the stress response.…”

“…12,17 We have recently shown that Isx-9 is able to protect adult rats from the decline in hippocampal cell proliferation and differentiation that normally result from procedural stress. 19 In the present work we seek to determine if Isx-9 will have therapeutic benefits for animals exposed to either acute or mild chronic umpredictable stress (CUS) both of which have been reported to impair hippocampal neurogenesis and related behaviors. 18 To determine whether Isx-9 was able to potentiate adult hippocampal neurogenesis in models of stress, we first evaluated its effects in animals that were exposed to repeated restraint stress (45 min/day, 7 days).…”

“…19 Indeed, the fact that no significant differences in hippocampal cell proliferation and neuronal differentiation were noted between the groups submitted to either restraint stress or mild CUS (and daily injections of Isx-9 and/or BrdU) and the control group (not submitted to stress but submitted to daily injections of Isx-9 and/or BrdU), may be due to the fact that daily experimental manipulations (i.e., animal handling and repeated i.p. injections), to which all groups were submitted to, could be acting as a potential stressor on hippocampal cell proliferation and neuronal commitment.…”