Adult Hippocampal Neurogenesis in the Human Brain: Updates, Challenges, and Perspectives.

The existence of neurogenesis in the adult human hippocampus has been under considerable debate within the past three decades due to the diverging conclusions originating mostly from immunohistochemistry studies. While some of these reports conclude that hippocampal neurogenesis in humans occurs throughout physiologic aging, others indicate that this phenomenon ends by early childhood. More recently, some groups have adopted next-generation sequencing technologies to characterize with more acuity the extent of this phenomenon in humans. Here, we review the current state of research on adult hippocampal neurogenesis in the human brain with an emphasis on the challenges and limitations of using immunohistochemistry and next-generation sequencing technologies for its study.

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions.

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS-induced by limited bedding and nesting material during the first week of life (postnatal days [P]2-9) on microglial (i) morphology; (ii) hippocampal gene expression; and (iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to control microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.

Impact of executive dysfunctions on episodic memory abilities in patients with ruptured aneurysm of the anterior communicating artery.

Executive and memory dysfunctions are among the most frequently reported deficits following a ruptured aneurysm of the anterior communicating artery (ACoA). In order to study the impact of the dysexecutive syndrome on episodic and semantic memory, the data obtained from 59 ACoA patients were examined retrospectively. All patients were assessed on a variety of episodic memory tests (Rey Auditory-Verbal Learning Test, Rey Complex Figure Test, Weschler Memory Scale), semantic memory (verbal fluency), and standardized tests of executive functions (Trail Making Test, Maze tests, Wisconsin Card Sorting Test). There was a strong positive correlation between executive dysfunction and retrieval difficulties in episodic and semantic memory tasks. Comparisons of subgroups of patients with high and low frontal lobe functioning on delayed recall and recognition revealed a significant group X condition interaction in addition to significant group and condition main effects. ACoAs patients with low frontal lobe functioning were particularly deficient in free recall (immediate and delayed) while recognition was equally well preserved in the two subgroups. Neither subgroup presented with an abnormal forgetting over time suggesting a retrieval deficit rather than a true retention impairment.