Neuroplasticity-related correlates of environmental enrichment combined with physical activity differ between the sexes

Abstract

Environmental enrichment (EE), comprising positive physical (exercise) and cognitive stimuli, influences neuronal structure and usually improves brain function. The promise of EE as a preventative strategy against neuropsychiatric disease is especially high during early postnatal development when the brain is still amenable to reorganization. Despite the fact that male and female brains differ in terms of connectivity and function that may reflect early life experiences, knowledge of the neural substrates and mechanisms by which such changes arise remains limited. This study compared the impact of EE combined with physical activity on neuroplasticity and its functional consequences in adult male and female rats; EE was provided during the first 3 months of life and our analysis focused on the hippocampus, an area implicated in cognitive behavior as well as the neuroendocrine response to stress. Both male and female rats reared in EE displayed better object recognition memory than their control counterparts. Interestingly, sex differences were revealed in the effects of EE on time spent exploring the objects during this test. Independently of sex, EE increased hippocampal turnover rates of dopamine and serotonin and reduced expression of 5-HT 1A receptors; in addition, EE upregulated expression of synaptophysin, a presynaptic protein, in the hippocampus. As compared

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“…Non-spatial working memory was assessed with the NOR test [12,15,16]. While there were no significant treatment effects during the first NOR training session, a significant treatment effect was observed in the second test session: low TPC and high SID doses increased the total exploration time of both objects, whereas high TPC and low SID treatments had no effect on this parameter.…”

“…In this study, the OF novelty test was used as a proxy for the estimation of anxiety [12,13]. TPC administration, in both low and high doses, exerted an anxiolytic effect by increasing exploratory behavior and inducing more center entries.…”

“…On the first day of behavioral testing, 30 min after TPC, SID or vehicle administration, all animals were tested in the open field. The OF test was used to measure locomotor and exploratory behavior (horizontal and vertical counts, respectively) and center entries as an index of anxiety in mice [12,13]. The OF was a plexiglass chamber (W40 × D40 × H40; Med Assoc., Fairfax, VT, USA) with automatic movement detection.…”

“…On the second day of behavioral testing, the NOR test was used to assess non-spatial working memory, a component of cognition [12,15]. Animals were left to familiarize themselves with the testing room for 1 h, and were then introduced into the NOR apparatus, which consisted of the open field (OF, described above) with the addition of bedding in order to mimic the familiar cage environment, as well as 2 objects placed near the two corners of the open field.…”

“…Between the two trials, all mice received either SID, TPC or vehicle, with a 6-h inter-trial interval. This version of the NOR, which depends on the functional integrity of the hippocampus [16], has previously been used to detect sex differences in the effects of enriched environment [12,57]. During Trial 1 (T1), the two objects in the arena were identical, and the time spent exploring them was recorded.…”