Ndel1 and Reelin Maintain Postnatal CA1 Hippocampus Integrity

How the integrity of laminar structures in the postnatal brain is maintained impacts neuronal functions. Ndel1, the mammalian homolog of NuDE from the filamentous fungus Aspergillus nidulans, is an atypical microtubule (MT)-associated protein that was initially investigated in the contexts of neurogenesis and neuronal migration. Constitutive knock-out mice for Ndel1 are embryonic lethal, thereby necessitating the creation a conditional knock-out to probe the roles of Ndel1 in postnatal brains. Here we report that CA1 pyramidal neurons from mice postnatally lacking Ndel1 (Ndel1 conditional knock-out) exhibit fragmented MTs, dendritic/synaptic pathologies, are intrinsically hyperexcitable and undergo dispersion independently of neuronal migration defect. Secondary to the pyramidal cell changes is the decreased inhibitory drive onto pyramidal cells from interneurons. Levels of the glycoprotein Reelin that regulates MTs, neuronal plasticity, and cell compaction are significantly reduced in hippocampus of mutant mice. Strikingly, a single injection of Reelin into the hippocampus of Ndel1 conditional knock-out mice ameliorates ultrastructural, cellular, morphological, and anatomical CA1 defects. Thus, Ndel1 and Reelin contribute to maintain postnatal CA1 integrity.1112Ysciescopu

Complex Risks from Old Urban Waste Landfills: Sustainability Perspective from Iasi, Romania

Landfills continue to represent the most frequent managerial practice for municipal solid wastes and an increasing and complex problem globally. In certain countries, a transition to an open society and free market is superimposed on the transition to sustainability, resulting in even higher complexity of management. This paper proposes an approach for problem-structuring of landfills in complex transitions: sustainability or unsustainability of a management approach is determined by a set of sustainability filters that are defined by sets of indicators and prioritized according the systemic concept of sustainability, which says that economy is embedded in society, which is embedded in nature. The writers exercise this approach with an old landfill in Iasi, Romania, and conclude for unsustainability, because the ecological sustainability filter is not successfully passed. Social and economic sustainability filters are also discussed in relation with the ecological sustainability indicators. The described approach allows a coherent, transdisciplinary synthesis of knowledge scattered across various disciplines, a pervasive problem in landfill management. The case study helps distinguish between generally true and context-dependent aspects.Peer reviewe

Reelin Improves Cognition and Extends the Lifespan of Mutant Ndel1 Mice with Postnatal CA1 Hippocampus Deterioration

The glycoprotein Reelin maintains neuronal positioning and regulates neuronal plasticity in the adult brain. Reelin deficiency has been associated with neurological diseases. We recently showed that Reelin is depleted in mice with a targeted disruption of the Ndel1 gene in forebrain postnatal excitatory neurons (Ndel1 conditional knockout (CKO)). Ndel1 CKO mice exhibit fragmented microtubules in CA1 pyramidal neurons, profound deterioration of the CA1 hippocampus and a shortened lifespan (similar to 10 weeks). Here we report that Ndel1 CKO mice (of both sexes) experience spatial learning and memory deficits that are associated with deregulation of neuronal cell adhesion, plasticity and neurotransmission genes, as assessed by genome-wide transcriptome analysis of the hippocampus. Importantly, a single injection of Reelin protein in the hippocampus of Ndel1 CKO mice improves spatial learning and memory function and this is correlated with reduced intrinsic hyperexcitability of CA1 pyramidal neurons, and normalized gene deregulation in the hippocampus. Strikingly, when treated with Reelin, Ndel1 CKO animals that die from an epileptic phenotype, live twice as long as nontreated, or vehicle-treated CKO animals. Thus, Reelin confers striking beneficial effects in the CA1 hippocampus, and at both behavioral and organismal levels.11Nsciescopu