Maternal separation prior to neonatal hypoxia-ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus

Exposure 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

The diagnostic validity of neuropsychological assessment in illiterate older adults

In the current study we explored the neuropsychological test performance of cognitively healthy illiterate individuals (i.e., without dementia) and their literate counterparts, as well as their literate peers with cognitive impairment, to identify useful tools for the clinical assessment of illiterate individuals. The main purpose of the study was to investigate the appropriateness of cognitive tasks in the diagnostic assessment of older illiterate individuals. The sample of this cross-sectional study included 1794 older adults, all participants of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study in Greece. The participants were divided in groups (cognitively healthy or with cognitive impairment) according to their level of functioning (high-low) and their educational level (attended formal schooling or not). A comprehensive neuropsychological battery was administered evaluating memory (verbal and visual), visuospatial perception, attention/information processing speed, executive functioning (switching, inhibition and cognitive flexibility) and language skills. The healthy illiterate cohort was at a disadvantage relative to the literate group on all variables (p’s .002). Moreover, only word list learning immediate and delayed free recall and delayed cued recall differentiated the healthy illiterate from the cognitive impairment literate group, favoring the former (p’s .002), ενώ στις υπόλοιπες δοκιμασίες που εξετάστηκαν οι αναλφάβητοι συμμετέχοντες είχαν χαμηλότερη επίδοση από τους εγγράμματους (όλα τα p .002), με εξαίρεση την άμεση και καθυστερημένη ελεύθερη ανάκληση και την καθυστερημένη ανάκληση με υποδείξεις λίστας λέξεων (όλα τα p < .002), στις οποίες υπερτερούσαν τα υγιή αναλφάβητα άτομα. Με βάση τα παρόντα ευρήματα, η επίδοση σε ορισμένες μεταβλητές σε έργο λεκτικής μνήμης υποδεικνύει την ύπαρξη ή μη γνωστικού ελλείμματος ανεξάρτητα από το εκπαιδευτικό επίπεδο, ενώ με βάση τις υπόλοιπες μεταβλητές που εξετάστηκαν υποτιμάται η επίδοση των γνωστικά υγιών αναλφάβητων ατόμων, γεγονός το οποίο μπορεί να οδηγήσει σε εσφαλμένη διάγνωση νοητικής έκπτωσης κατά την κλινική εκτίμηση σε αυτή την ομάδα. Επομένως, αναδεικνύεται η ανάγκη δημιουργίας διαφορετικού τρόπου εξέτασης με μεγαλύτερη οικολογική εγκυρότητα, καθώς και κανονιστικών τιμών για την εκτίμηση της νοητικής κατάστασης των ηλικιωμένων αναλφάβητων ατόμων