hif-1 plays a role in hypoxia-induced gustatory plasticity of Caenorhabditis elegans.

Background: Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor in the detection of low oxygen levels, inducing expression of genes involved in mediating the response to hypoxia to maintain cellular oxygen homeostasis. Caenorhabditis elegans is a soil nematode that has evolved specialized chemosensory neurons that detect changes in oxygen levels and guide its behaviour and responses to food. The role of the hif-1 gene in modifying chemosensory behaviour in response to chemical hypoxia however remains unclear. Furthermore, the role of epigenetic modifiers in mediating this behavioural response to hypoxia is unclear. Aims: Our study addresses two questions (a) Do hypoxia-mimetics modify worm behaviour and (b) Are these behaviours modulated by HIF-dependent expression of epigenetic regulators? Material and methods: This study used established behavioural paradigms in hif-1 mutant strains of C. elegans, to study responses to chemical hypoxia. Results: We show that exposure to the hypoxia-mimetic, sodium sulphite, changes the gustatory responses, chemotaxis, gustatory plasticity and associative conditioning behaviour. Longer-term exposure to hypoxia changes the behavioural response of wild type C. elegans, mediated by the HIF pathway. Epigenetic modifiers, lithium chloride and valproic acid, further modulate these behavioural responses.

Caenorhabditis elegans: A Model for Studying Human Pathogen Biology.

Novel clinical strategies need to be evolved, as pathogens, especially the ones that infect the human, develop resistance. To do so, host pathogen biology needs to be clearly understood and this can be done using a nematode worm, Caenorhabditis elegans, which harbours the same virulent microbes. Over several decades, the worm has been used to study host-microbe interaction with reference to immune response of the worm, antimicrobial molecules secreted, cell death in the worm body, quorum sensing network of the bacteria and fast or slow worm death. This mini review gives a bird's eye view of the directions that have been taken in these areas to date. Currently, the worm has been proposed to be an ideal model for high throughput screening of natural and synthetic drugs against a variety of bacteria. Experimental systems that allow this screening have been patented. Caenorhabditis elegans, thus, is one of the very effective models for studying pathogens that infect human.

Lithium affects histogenesis of embryonic chick retina.

BACKGROUND: Lithium, a drug used extensively for treatment of bipolar disorders, has also been shown to be neuroprotective in vivo and in vitro. While gross teratogenic effects of lithium at higher doses have been reported, in view of its potential wider use, it is necessary to investigate its effects on tissue formation at relatively low doses of lithium where no apparent teratogenic effects on morphology are observed. MATERIALS AND METHODS: We have used retina of chick embryo to investigate its effects during neural histogenesis. Three major cellular events involved in retinal histogenesis have been monitored: Proliferation as measured by expression of proliferating cell nuclear antigen (PCNA); initiation of differentiation as observed by expression of p27/Kip1 expression; apoptosis as monitored by TdT-mediated dUTPX-nick end labeling. RESULT: We demonstrate that lithium at a dose of 60 mM has no effect on gross eye morphology; it disrupts histogenesis of chick retina by blocking proliferation, inducing apoptosis, and generating post mitotic cells prematurely.

Differential display RT-PCR reveals genes associated with lithium-induced neuritogenesis in SK-N-MC cells.

Lithium is shown to be neurotrophic and protective against variety of environmental stresses both in vitro as well as in vivo. In view of the wider clinical applications, it is necessary to examine alterations in levels of expression of genes affected by lithium. Lithium induces neuritogenesis in human neuroblastoma cell line SK-N-MC. Our aim was to elucidate genes involved in lithium-induced neuritogenesis using SK-N-MC cells. The differential display reverse transcriptase polymerase chain reaction (DD-RT-PCR) technique was used to study gene expression profiles in SK-N-MC cells undergoing lithium-induced neuritogenesis. Differential expression of genes in control and lithium (2.5 mM, 24 h)-treated cells was compared by display of cDNAs generated by reverse transcription of mRNA followed by PCR using arbitrary primers. Expression of four genes was altered in lithium-treated cells. Real-time PCR was done to confirm the levels of expression of each of these genes using specific primers. Lithium significantly up-regulated NCAM, a molecule known to stimulate neuritogenesis, occludin, a molecule participating in tight junctions and PKD2, a molecule known to modulate calcium transport. ANP 32c, a gene whose function is not fully known yet, was found to be down-regulated by lithium. This is the first report demonstrating altered levels of expression of these genes in lithium-induced neuritogenesis and contributes four hitherto unreported candidates possibly involved in the process.

A brief review of in vitro models of diabetic neuropathy.

The neuropathies of the peripheral, central and autonomic nervous systems are known to be caused by hyperglycemia, a consequence of the deregulation of glucose in diabetes. Several in vivo models such as streptozotocin-induced diabetic rats, mice and Chinese hamsters have been used to study the pathogenesis of diabetic neuropathy because of their resemblance to human pathology. However, these in vivo models have met with strong ethical oppositions. Further, the system complexity has inherent limitations of inconvenience of analyzing ephemeral molecular events and crosstalk of signal transduction pathways. Alternative in vitro models have been selected and put to effective use in diabetic studies. We critically review the use of these in vitro models such as primary cultures of dorsal root ganglia, Schwann cells and neural tissue as well as neural cell lines which have proved to be excellent systems for detailed study. We also assess the use of embryo cultures for the study of hyperglycemic effects on development, especially of the nervous system. These systems function as useful models to scrutinize the molecular events underlying hyperglycemia-induced stress in neuronal systems and have been very effectively used for the same. This comprehensive overview of advantages and disadvantages of in vitro systems that are currently in use will be of interest especially for comparative assessment of results and for appropriate choice of models for experiments in diabetic neuropathy.

An unusual member of the Cdk family: Cdk5.

The proline-directed serine threonine kinase, Cdk5, is an unusual molecule that belongs to the well-known large family of proteins, cyclin-dependent kinases (Cdks). While it has significant homology with the mammalian Cdk2 and yeast cdc2, unlike the other Cdks, it has little role to play in cell cycle regulation and is activated by non-cyclin proteins, p35 and p39. It phosphorylates a spectrum of proteins, most of them associated with cell morphology and motility. A majority of known substrates of Cdk5 are cytoskeletal elements, signalling molecules or regulatory proteins. It also appears to be an important player in cell-cell communication. Highly conserved, Cdk5 is most abundant in the nervous system and is of special interest to neuroscientists as it appears to be indispensable for normal neural development and function. In normal cells, transcription and activity of Cdk5 is tightly regulated. Present essentially in post-mitotic neurons, its normal activity is obligatory for migration and differentiation of neurons in developing brain. Deregulation of Cdk5 has been implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. Regulators of Cdk5 activity are considered as potential therapeutic molecules for degenerative diseases. This review focuses on the role of Cdk5 in neural cells as regulator of cytoskeletal elements, axonal guidance, membrane transport, synaptogenesis and cell survival in normal and pathological conditions.