The Role of Osteopontin in the Peripheral and Central Nervous Systems

The glycoprotein osteopontin (OPN) is a secreted and heavily phosphorylated peptide that plays a role in a variety of cellular processes from cell adhesion to apoptosis. These actions are principally thought to be mediated via interactions with CD44.and integrins. OPN is expressed in a wide variety of tissues including the peripheral and central nervous systems (PNS and CNS respectively), although its exact function in these tissues remains unclear. We identified OPN as a putative axotomy response gene from a previously generated dorsal root ganglia (DRG) subtractive cDNA library. Immunohistochemical ,staining demonstrated that OPN protein colocalises with neurofilament but not other nociceptive markers. Mechanosensory thresholds in osteopontin knockout (OPN KO) animals are significantly increased compared to wild-type (WT) controls, although there are no differences in allodynia between genotypes after a spared nerve injury (SNI) model of neuropathic pain. Moreover, exogenous recombinant OPN has no effect on neurite outgrowth from adult WT sensory neurons, and no differences in neurite outgrowth were observed in OPN KO animals compared to WT controls. Within the CNS, previous studies have demonstrated that OPN expression increases in a number of cell types after injury, although its precise function is equivocal. Here, I demonstrate that organotypic hippocampal OPN KO cultures display increased apoptosis following glutamate induced cell death compared to WT controls. Moreover, exogenous recombinant OPN is neuroprotective to OPN KO and WT cultures. This neuroprotective effect is integrin mediated and involves activation ofthe Akt and ERK pathways. In summary, these studies further extend our understanding of the neuroprotective and possible cell survival roles played by OPN in the nervous system. Further studies are now warranted to extend those presented here and define the mechanisms that underlie the observed effects thus far delineated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Energetic state during learning affects foraging choices in starlings

We investigated the influence of energetic state at the time of acquaintance with a new food source on preference for that source on later encounters, using wild-caught European starlings as subjects. Twelve birds learned to obtain food rewards by pecking at either of two keys identified by color. The keys were encountered in different sessions, while the subjects were food deprived or prefed. Food rewards from both sources were always identical. After an equal number of reinforced trials with each source, the birds were presented with choices between them. The birds significantly preferred the source that had previously delivered food under higher deprivation. We relate these results to findings reported elsewhere of preferences for options previously associated with greater effort. We hypothesize that subjects may attribute value to an option according to the marginal fitness gain associated with this option in the past. Although this process may be adaptive under many circumstances, it violates the assumptions of normative models of choice that imply mechanisms of valuation sensitive to the absolute properties of a payoff or to expected absolute changes in state. Copyright 2004.foraging; hunger; starlings; state-dependent choice

Galanin acts as a neuroprotective factor to the hippocampus

The expression of the neuropeptide galanin is markedly up-regulated in many areas of the central and peripheral nervous system after injury. We have recently demonstrated that peripheral sensory neurons depend on galanin for neurite extension after injury, mediated by activation of the second galanin receptor subtype (GALR2). We therefore hypothesized that galanin might also act in a similar manner in the CNS, reducing cell death in hippocampal models of excitotoxicity. Here we report that galanin acts an endogenous neuroprotective factor to the hippocampus in a number of in vivo and in vitro models of injury. Kainate-induced hippocampal cell death was greater in both the CA1 and CA3 regions of galanin knockout animals than in WT controls. Similarly, exposure to glutamate or staurosporine induced significantly more neuronal cell death in galanin knockout organotypic and dispersed primary hippocampal cultures than in WT controls. Conversely, less cell death was observed in the hippocampus of galanin overexpressing transgenic animals after kainate injection and in organotypic cultures after exposure to staurosporine. Further, exogenous galanin or the previously described high-affinity GALR2 agonist, both reduced cell death when coadministered with glutamate or staurosporine in WT cultures. These results demonstrate that galanin acts an endogenous neuroprotective factor to the hippocampus and imply that a galanin agonist might have therapeutic uses in some forms of brain injury