Biomedical subjects

Lisa A Teather

Publications and source records attributed to Lisa A Teather.

6 recordsLinked to original sources

PubMed2003

Cyclooxygenase-2 mediates platelet-activating factor-induced prostaglandin E2 release from rat primary astrocytes.

The phospholipid mediator platelet-activating factor (PAF), and its non-hydrolyzable analog methylcarbamyl-PAF (mc-PAF) increase prostaglandin E(2) (PGE(2)) release from astrocyte-enriched cortical cell cultures. Cyclooxygenase (COX) enzymes--of which there are two known isoforms--convert arachidonic acid to prostaglandin (PG) H(2) (PGH(2)), which is further metabolized to various PGs, including PGE(2). COX-1 is generally considered to contribute to cell homeostasis, whereas COX-2 is thought to mediate inflammatory/immune PG formation. In this study we examined the involvement of the COX isoforms in PAF-induced PGE(2) release. Treatment of cells with the non-specific COX inhibitor indomethacin, or the specific COX-2 inhibitor NS-398, prior to mc-PAF stimulation completely blocked the PAF-induced release of PGE(2); treatment with more selective COX-1 inhibitors (i.e. piroxicam and SC-560) failed to significantly do so. These data suggest that COX-2 is responsible for PAF-mediated PGE(2) release in primary astrocytes.

Animals↗

PubMed2003

Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats.

The present study was designed to assess the effect of supplementation with dietary cytidine (5')-diphosphocholine (CDP-choline), a source of cytidine and choline, on memory in young and older rats. Although the hippocampal-dependent memory deficits in aged rats are well documented, cognitive functioning in early aging has not been as thoroughly evaluated. Female Sprague-Dawley rats (3 or 15 months of age) consumed either a control diet or a diet supplemented with CDP-choline (approximately 500 mg/kg/day) for 8 weeks, after which they were trained to perform spatial and cued versions of the Morris water maze. Compared with young rats, aged rats exhibited a selective deficit in spatial memory tasks that required rats to retain information for 24 h or longer. CDP-choline supplementation protected against the development of this deficit, but had no memory-enhancing effect in normal young rats. These findings suggest that early-aged rats display a selective impairment in hippocampal-dependent long-term memory, and that dietary CDP-choline supplementation can protect against this deficit.

Administration, Oral↗

PubMed2002

Platelet-activating factor increases prostaglandin E(2) release from astrocyte-enriched cortical cell cultures.

The phospholipid mediator platelet-activating factor (PAF) increased the release of prostaglandin E(2) (PGE(2)) from astrocyte-enriched cortical cell cultures in a concentration- and time-dependent manner. The nonhydrolyzable PAF analog methylcarbamyl-PAF (mc-PAF), the PAF intermediate lyso-PAF, and arachidonic acid (AA) also produced this effect. In contrast, phosphatidlycholine (PC) and lyso-PC, lipids that are structurally similar to PAF and lyso-PAF, had no effect on PGE(2) production, suggesting that PAF-induced PGE(2) release is not the consequence of nonspecific phospholipid-induced membrane perturbation. Antagonism of intracellular PAF binding sites completely abolished the ability of mc-PAF and lyso-PAF to mobilize PGE(2,) and attenuated the AA effect. Antagonism of the G-protein-coupled PAF receptor in plasma membranes had no significant effect on mc-PAF, lyso-PAF or AA-induced PGE(2) release. Based on the present findings, we hypothesize that intracellular PAF is a physiologic stimulus of PGE(2) production in astrocytes.

Animals↗

PubMed2002

Platelet-activating factor antagonists decrease the inflammatory nociceptive response in rats.

RATIONALE: Platelet-activating factor (PAF) is a membrane-derived phospholipid mediator that has biological effects on a variety of cells and tissues. A variety of stimuli, including those producing inflammation, promote the synthesis and release of PAF from various cell types. Evidence suggests that PAF exerts cellular actions through a plasma membrane receptor as well as via intracellular (microsomal) PAF binding sites. OBJECTIVE: The present study was designed to: 1) investigate the role of PAF in a model of inflammatory nociception in rats (i.e. the formalin test), and 2) localize PAF's site(s) of action in nociception. To do this, we assessed the effect of administering two PAF antagonists (BN 52021 and BN 50730, which are selective for cell surface and intracellular PAF binding sites, respectively) on formalin-induced nociceptive responses. METHODS: Forty minutes prior to formalin injection into the rat hindpaw, male Sprague-Dawley rats received systemic injections of BN 52021 (10, 1, or 0.1 mg/kg), BN 50730 (10, 1, or 0.1 mg/kg), or vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water, HBC) and the effects of the drugs on nociceptive behavioral responses were measured. RESULTS: Rats receiving systemic BN 52021 or BN 50730 displayed a significant reduction of nociceptive responses in the late, but not early, phase of formalin-induced nociception. CONCLUSIONS: These findings suggest a role for endogenous PAF in nociceptive transmission, especially for persistent pain such as that which occurs in the late phase of the formalin test. The findings also indicate that both intracellular and cell surface PAF binding sites are involved in nociceptive modulation in rats, and that PAF antagonists might be useful for treating some patients with acute or chronic pain.

Animals↗

PubMed2002

Environmental conditions influence hippocampus-dependent behaviours and brain levels of amyloid precursor protein in rats.

Sprague-Dawley rats were reared in enriched (EC; group housing, exposure to stimulating objects, frequent handling) or restricted (RC; individual housing, no exposure to stimulating objects, minimal handling) environments starting on day 23 of life. At six months of age, they underwent behavioural tests to assess 'cognitive' and 'stimulus-response' memory, selective attention, and inflammatory pain processing. Alterations in synapses and cell survival may occur as a result of environment differences; therefore we assessed the brain levels of several proteins implicated in neurite outgrowth, synaptogenesis, and cell survival. Brains were dissected and analysed for amyloid precursor protein (APP) and other synaptic and cytoskeletal proteins using Western blotting. The performance of EC animals in a hidden platform water maze task, and in a test of selective attention (both of which are thought to involve the hippocampus) was superior to that of RC animals. In contrast, performance of RC animals on two stimulus-response tasks, the visible platform water maze test and simple visual discrimination (both of which are thought to be hippocampal independent) was indistinguishable from that of EC animals. Male EC rats displayed a different behavioural response to formalin during the inflammatory phase of nociception--the phase affected by hippocampal processing; a similar trend was observed in females. Female but not male RC rats exhibited elevated plasma corticosterone levels; adrenal weights were unaffected by environmental conditions. Region-specific increases in brain levels of APP, neurofilament-70 (NF-70), and platelet-activating factor receptor (PAF-R) were found in EC rats. These data suggest that enriched animals manifest enhanced functioning of certain hippocampus-mediated behaviours when compared with that of their restricted counterparts; and that brain levels of various synaptic and structural proteins involved in neurite outgrowth, cell survival, and synaptogenesis, are affected by environmental factors.

Amyloid beta-Protein Precursor↗

PubMedDate not supplied

Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation.

Evidence indicates that prostanoids, such as prostaglandins, play a regulatory role in several forms of neural plasticity, including long-term potentiation, a cellular model for certain forms of learning and memory. In these experiments, the significance of the COX isoforms cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in post-training memory processes was assessed. Adult male Long-Evans rats underwent an eight-trial (30-sec intertrial interval) training session on a hippocampus-dependent (hidden platform) or dorsal striatal-dependent (visible platform) tasks in a water maze. After the completion of training, rats received an intraperitoneal injection of the nonselective COX inhibitor indomethacin, the COX-1-specific inhibitor piroxicam, the COX-2-specific inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]-methanesulfonamide (NS-398), vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water), or saline. On a two-trial retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In the hidden platform task, the retention test escape latencies of rats administered indomethacin (5 and 10 mg/kg) or NS-398 (2 and 5 mg/kg) were significantly higher than those of vehicle-treated rats, indicating an impairment in retention. Injections of indomethacin or NS-398 that were delayed 2 h post-training had no effect on retention. Post-training indomethacin or NS-398 had no influence on retention of the visible platform version of the water maze at any of the doses administered. Furthermore, selective inhibition of COX-1 via post-training piroxicam administration had no effect on retention of either task. These findings indicate that COX-2 is a required biochemical component mediating the consolidation of hippocampal-dependent memory.

Animals↗