 We examined the interaction between MS and ΝΗΙ on emotionality and markers of plasticity. Both MS and NHI increased anxiety levels, but only NHI induced depressionlike behavior. Maternal separation did not further increase emotionality in HI-treated rats. Both MS and NHI decreased synaptophysin levels in dentate gyrus and CA3 hippocampal areas. BDNF expression in CA3 was decreased only in the HI animals that were maternally-separated. AbstractExposure to early-life stress is associated with long-term alterations in brain and behavior, and may aggravate the outcome of neurological insults. This study aimed at investigating the possible interaction between maternal separation, a model of early stress, and subsequent neonatal hypoxia-ischemia on emotional behavior and markers of synaptic plasticity in hippocampus. Therefore, rat pups (N=60) were maternally separated for a prolonged (MS 180min) or a brief (MS 15min) period during the first six postnatal days, while a control group was left undisturbed. Hypoxia-ischemia was applied to a subgroup of each rearing condition on postnatal day 7. Emotional behavior was examined at three months of age and included assessments of anxiety (elevated plus maze), depression-like behavior (forced swimming) and spontaneous exploration (open field). Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in CA3 and dentate gyrus hippocampal regions. We found that neonatal hypoxia-ischemia caused increased levels of anxiety, depression-like behavior and locomotor activity (ambulation). Higher anxiety levels were also seen in maternally separated rats (MS180min) compared to non-maternally separated rats, but prolonged maternal separation prior to HI did not potentiate the HI-associated effect. No differences among the three rearing conditions were found regarding depression-like behavior or ambulation. Immunohistochemical evaluation of synaptophysin revealed that both prolonged maternal separation (MS180min) and neonatal hypoxia-ischemia significantly reduced its expression in the CA3 and dentate gyrus. Decreases in synaptophysin expression in these areas were not exacerbated in rats that were maternally separated for a prolonged period prior to HI. Regarding BDNF expression, we found a significant decrease in immunoreactivity only in the hypoxic-ischemic rats that were subjected to the prolonged maternal separation paradigm. The above findings suggest that early-life stress prior to neonatal hypoxia-ischemia leads to significant alterations in synaptic plasticity of the dorsal hippocampus during adulthood, but does not exacerbate HI-related changes in emotional behavior.

Objectives: We investigated the utility of traditional neuropsychological tests in older uneducated/illiterate individuals without dementia to determine the possibility that they are likely not appropriate for this group. Methods: We assessed the neuropsychological performance of 1122 older adults [≥65 years old; mean age: 74.03 (SD = 5.46); mean education: 4.76 (SD = 2.5) years; women: n = 714], in the context of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), a population-based study conducted in Greece. Results: We based our analyses on three groups: high-functioning/cognitively healthy (i.e., without dementia) uneducated/illiterate individuals (n = 80), high-functioning/cognitively healthy educated/literate individuals (n = 932), and low-functioning/cognitively impaired educated/literate individuals (presumably with dementia; n = 110). We used binary regression analyses with Bonferroni correction to investigate whether test performance differentiated uneducated/illiterate from educated/literate individuals. Models were adjusted for age and sex; raw test scores were the predictor variables. The uneducated/illiterate cohort was at a disadvantage relative to the healthy educated/literate group on all variables but verbal memory recognition and consolidation, congruent motor responses, and phonological fluency clustering (p > .002). Moreover, only word list learning immediate and delayed free recall and delayed cued recall differentiated the high-functioning/cognitively healthy uneducated/illiterate from the low-functioning/cognitively impaired educated/literate group, favoring the former (p’s < .002). Conclusions: Our findings suggest that only particular verbal memory test variables are fair in determining whether older uneducated/illiterate individuals have functional/cognitive impairment suggestive of a neurodegenerative process. On all other neuropsychological variables, this cohort was at a disadvantage. Therefore, we highlight the need for identifying appropriate methods of assessment for older uneducated/illiterate individuals.