Microglial activation induces neuronal death in Chandipura virus infection

Neurotropic viruses induce neurodegeneration either directly by activating host death domains or indirectly through host immune response pathways. Chandipura Virus (CHPV) belonging to family Rhabdoviridae is ranked among the emerging pathogens of the Indian subcontinent. Previously we have reported that CHPV induces neurodegeneration albeit the root cause of this degeneration is still an open question. In this study we explored the role of microglia following CHPV infection. Phenotypic analysis of microglia through lectin and Iba-1 staining indicated cells were in an activated state post CHPV infection in cortical region of the infected mouse brain. Cytokine Bead Array (CBA) analysis revealed comparatively higher cytokine and chemokine levels in the same region. Increased level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Nitric Oxide (NO) and Reactive Oxygen species (ROS) in CHPV infected mouse brain indicated a strong inflammatory response to CHPV infection. Hence it was hypothesized through our analyses that this inflammatory response may stimulate the neuronal death following CHPV infection. In order to validate our hypothesis supernatant from CHPV infected microglial culture was used to infect neuronal cell line and primary neurons. This study confirmed the bystander killing of neurons due to activation of microglia post CHPV infection

Effects of early life starvation stress on adult foraging behavior in «Caenorhabditis elegans»

The work presented in this thesis explores the effect of early-life starvation stress on adult foraging behavior in the nematode C. elegans. When faced with stringent environmental conditions like scarcity of food in early larval stages, C. elegans go into an arrested developmental stage called dauer from which they can recover when food becomes available again. We examined if the characteristic foraging behavior seen in C. elegans adults are in any way changed in animals experiencing dauer earlier in their lifetime. We established that post-dauer animals show reduced exploratory foraging behavior and that this behavioral plasticity in response to early life stress is seen in a wild isolate, CB4856 but not in the lab-adapted N2 strain.L' étude présentée dans cette thèse explore les effets du stress de privation de nourriture chez le jeune C. elegans sur son comportement de recherche de nourriture à l'âge adulte. Lorsqu'il fait face à des conditions environnement difficiles telles que la rareté de la nourriture lors de premiers stades larvaires, C. elegans entre dans une stase de développement nommée stade dauer, dont ils peuvent en sortir lorsque la nourriture redevient disponible. Nous avons évalué dans quelle mesure les caractéristiques du comportement de recherche de nourriture observes chez C. elegans adulte sont affectées chez les animaux ayant traversé le stade dauer au cours des phases précoces de leur vie. Nous avons dmontr que les animaux post-dauer prsentent des comportements explorateurs réduits. Nous avons aussi montré cette plasticité comportementale, en réponse au stress précoce, observée chez le nématode sauvage isolé CB4856, est toutefois absente chez la lignée N2 adaptée aux laboratoires

A three-dimensional habitat for C. elegans environmental enrichment.

As we learn more about the importance of gene-environment interactions and the effects of environmental enrichment, it becomes evident that minimalistic laboratory conditions can affect gene expression patterns and behaviors of model organisms. In the laboratory, Caenorhabditis elegans is generally cultured on two-dimensional, homogeneous agar plates abundantly covered with axenic bacteria culture as a food source. However, in the wild, this nematode thrives in rotting fruits and plant stems feeding on bacteria and small eukaryotes. This contrast in habitat complexity suggests that studying C. elegans in enriched laboratory conditions can deepen our understanding of its fundamental traits and behaviors. Here, we developed a protocol to create three-dimensional habitable scaffolds for trans-generational culture of C. elegans in the laboratory. Using decellularization and sterilization of fruit tissue, we created an axenic environment that can be navigated throughout and where the microbial environment can be strictly controlled. C. elegans were maintained over generations on this habitat, and showed a clear behavioral bias for the enriched environment. As an initial assessment of behavioral variations, we found that dauer populations in scaffolds exhibit high-frequency, complex nictation behavior including group towering and jumping behavior