Hippocampal neurogenesis is impaired in Alzheimer’s disease (AD) patients and familial Alzheimer’s disease (FAD) mouse models. However, it is unknown whether new neurons play a causative role in memory deficits. Here, we show that immature neurons were actively recruited into the engram following a hippocampus-dependent task. However, their recruitment is severely deficient in FAD. Recruited immature neurons exhibited compromised spine density and altered transcript profile. Targeted augmentation of neurogenesis in FAD mice restored the number of new neurons in the engram, the dendritic spine density, and the transcription signature of both immature and mature neurons, ultimately leading to the rescue of memory. Chemogenetic inactivation of immature neurons following enhanced neurogenesis in AD, reversed mouse performance, and diminished memory. Notably, AD-linked App, ApoE, and Adam10 were of the top differentially expressed genes in the engram. Collectively, these observations suggest that defective neurogenesis contributes to memory failure in AD.

Immunohistological investigations have given rise to divergent perspectives about adult hippocampal neurogenesis in humans. Therefore, this study aimed to examine whether a comprehensive transcriptomic analysis of signature markers of neurogenesis, supplemented with markers of gliogenesis, vasculogenesis, cell proliferation, and apoptosis, may help discern essential aspects of adult hippocampal neurogenesis in humans. RNA expression data for salient marker genes of neurogenesis, gliogenesis, vasculogenesis, and apoptosis in post-mortem human hippocampal tissue [from prenatal (n = 15), child (n = 5), adolescent (n = 4), and adult (n = 6) brains] were downloaded from the Allen Human Brain Atlas database (http://www.brainspan.org/rnaseq/search/index.html). Gene expression data was categorized, median values were computed, and age group-specific differential expression was subjected to statistical analysis (significance level, α = 0.01). With the exception of the genes encoding GFAP, BLBP, SOX2, and PSA-NCAM (unchanged), and the post-mitotic late maturation markers CALB1, CALB2, MAP2, and NEUN as well as the pan-neuronal marker PROX1 which were persistently expressed throughout, expression of all other genes associated with neurogenesis was steeply and progressively downregulated between perinatal life and adulthood. Interestingly, expression of the classical proliferation marker KI67 and a progenitor cell marker TBR2 were found to have reached baseline expression levels (zero expression score) at adolescence while the expression of immature neuronal, post-mitotic early and late maturation markers remained at a constant level after childhood. In contrast, markers of gliogenesis (other than PDGFRA and Vimentin) were significantly upregulated between prenatal life and childhood. Expression of the vasculogenesis markers VEGFA and FGF2 did not differ across any of the age groups studied, whereas the expression of apoptotic markers was progressively decreased after prenatal life. Our findings indicate that the progression of neurogenesis from progenitor cells is highly restricted in the human brain from childhood onwards. An alternative possibility that limited neurogenesis may be continued in adolescents and adults from a developmentally arrested pool of immature neurons needs to be examined further through experimental studies.

Objective: The placenta connects and separates two genetically distinct individuals: the mother and the fetus. There is no placental-fetal barrier blocking lead transport, placing the fetus at high risk from lead exposure. The placenta has been investigated as a possible indicator of environmental exposures. Recent studies have been focused on the interaction between toxic and essential metals in placenta as there is little information on the levels of lead and essential metals in human placental tissue in Indian scenario. Material & Methods: The present study was designed to determine the status of lead and some essential metals in placental tissue of women residing in and around, Lucknow, India. Sixty pregnant women attending the local maternity home in the city were recruited to determine the concentrations of lead (toxic metal) and zinc, copper, iron & calcium (essential metals) using atomic absorption spectrophotometry. Results: The mean±SD levels of placental lead was 0.35 ± 0.30μg/g which is lower than those reported in Australia (0.56μg/g) & Poland (0.50μg/g), and slightly higher than Spain (0.11μg/g). The mean ± SD (range) of placental zinc, copper, iron & calcium was found to be 7.67± 2.99 μg/g (0.47-13.75), 1.03 ± 0.55 μg/g (0.49-3.41), 76.42 ± 20.13 μg/g (17.67-135.25), 90.46 ± 112.47 μg/g (1.77-420.5) respectively. On the basis of parity, placental lead level was significantly higher (p<0.05), while copper and zinc were significantly lower (p<0.05, p<0.01 respectively) in multipa-rous cases as compared to nulliparous. Placental lead levels had significant negative correlation with zinc levels (r= -0.35, p<0.05). Conclusion: The results suggested that increased lead level affect the essential metal level and its level increased with parity whereas, there was a depletion of maternal stores of essential elements (Zn, Cu, Fe and Ca) with increasing parity. Key Words: Placenta; Lead; Essential metals; parity; Atomic Absorption Spectrometer DOI: 10.3126/ajms.v1i2.3199Asian Journal of Medical Sciences 1 (2010) 32-36

Methylation of adenosines at N6 position (m6A) is the most frequent internal modification in mRNAs of the human genome and attributable to diverse roles in physiological development, and pathophysiological processes. However, studies on the role of m6A in neuronal development are sparse and not well-documented. The m6A detection remains challenging due to its inconsistent pattern and less sensitivity by the current detection techniques. Therefore, we applied a sliding window technique to identify the consensus site (5′-GGACT-3′) n ≥ 2 and annotated all m6A hotspots in the human genome. Over 6.78 × 10⁷ hotspots were identified and 96.4% were found to be located in the non-coding regions, suggesting that methylation occurs before splicing. Several genes, RPS6K, NRP1, NRXN, EGFR, YTHDF2, have been involved in various stages of neuron development and their functioning. However, the contribution of m6A in these genes needs further validation in the experimental model. Thus, the present study elaborates the location of m6A in the human genome and its function in neuron physiology.