Estradiol to aged female or male mice improves learning in inhibitory avoidance and water maze tasks

Abstract

Although 17β-Estradiol (E 2 ) improves cognitive performance of aged female mice, its mnemonic effects when administered post-training to aged male mice have not been examined. E 2 (10 µg, SC) or oil vehicle was administered to intact, 24-month-old female or male congenic (primarily C57BL/6 background) mice immediately after training in the inhibitory avoidance or water maze tasks. Following behavioral testing, effects of 1 or 24 h of E 2 exposure on hippocampal levels of E 2 and brain-derived neurotrophic factor (BDNF) were examined. Female and male mice administered E 2 showed significantly better performance in the inhibitory avoidance task than did vehicle-administered mice. When tested 24 h after training, mice that received E 2 had significantly longer latencies to cross-over to the shock-associated side of the chamber than did vehicleadministered mice. Female or male mice administered E 2 showed significantly better performance in the reference memory aspect of the spatial water maze task. When tested 30 min after training, mice administered E 2 had shorter latencies to, and spent longer swimming in, the quadrant that the hidden platform had previously been located in. E 2 administration produced physiological levels of E 2 in the hippocampus 1 and 24 h after E 2 . BDNF levels in the hippocampus were decreased following 1 h of E 2 exposure compared to vehicle. These findings suggest that E 2 to female and male mice may overcome age-related deficits in reference memory in an emotional or spatial learning task.

Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice

“…The inability of post-training estradiol to improve memory among aged females in this study stands in contrast to numerous reports in this age group in which chronic estradiol treatment improved various types of memory including spatial memory in the water maze (Frick et al, 2002;Frye, Rhodes & Dudek, 2005;Markham et al, 2002), radial arm maze (Heikkinen et al, 2002), and T-maze (Gibbs, 2000), object memory (Vaucher et al, 2002), and spontaneous alternation (Miller, Hyder, Assayag, Panarella, Tousignant & Franklin, 1999). However, all of these studies used either a more slowly metabolized form of estrogen (estradiol benzoate) or a much longer treatment duration (ranging from 3 weeks to 12 months), combined with the presence of estradiol in the circulation during testing.…”

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

“…Finally, for both estrogen and BDNF, the effects that have been observed exhibit unique and characteristic response patterns, that are not shared by any other humoral agent. Thus, estrogen has striking effects that range from alterations in behavior [5][6][7][8][9][10][11][12][13], structure (spine morphology, density, and spine synapses; Table 2), and physiology (potentiation of glutamatergic inputs in area CA1; Table 2) including specific receptormediated actions, such as actions at the NMDA receptor (although not exclusively; [14]). BDNF is the one other molecule that has been shown to exert many, if not all, of these same specific effects (Table 2).…”

“…This has been shown for male rats after manipulations that increase estradiol, and the reverse, that learning is worse when estradiol levels are low, for example in aromatase-knockout mice [42]. This has also been studied in female rats after ovariectomy and estradiol replacement, although it is difficult to compare some of these studies because doses of estradiol vary, as well as other potential factors such as age, time after ovariectomy, and housing [5][6][7][8][9][11][12][13]43]. The variability occurs not only in whether behavior is enhanced, but also the type of task.…”

“…The variability occurs not only in whether behavior is enhanced, but also the type of task. Thus, many studies of spatial learning (a classic hippocampal-dependent behavior) show an improvement after estradiol administration, but other types of memory can sometimes also improve, suggesting not only hippocampal effects but also non-hippocampal effects [5][6][7][8][9][11][12][13]43]. Learning appears to be enhanced on the morning of proestrus relative to other cycle stages or relative to ovariectomy [44].…”

Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks

“…The Morris Water Maze (San Diego Instruments, San Diego, CA, USA; 97 cm in diameter) was used according to previously described methods (Bennett, McRae, Levy, & Frick, 2006;Frye, Rhodes, & Dudek, 2005). Temperature of the water in the maze was 22-25 °C.…”