Effects of Intraventricular Locus Coeruleus Transplants on Seizure Severity in Genetically Epilepsy-Prone Rats Following Depletion of Brain Norepinephrine

Audiogenic seizures (AGS) in genetically epilepsy-prone rats (GEPR) of the moderateseizure substrain (GEPR-3s) were investigated to determine whether norepinephrine (NE) depletion induced by 6-hydroxydopalnine (6-OHDA) microinfusion into the locus coeruleus (LC) could alter the efficacy of intraventricular NE tissue grafts in promoting reductions in seizure severity in AGS. GEPR-3s were stereotaxically infused with 6-OHDA (4μg/side/rat), or vehicle into the region of the LC. Following 6-OHDA treatment all animals were subjected to 3 AGS tests. GEPR-3s seizure severities were increased in 39.5% of the animals after microinfusion of 6-OHDA into the region of the LC. Following the third AGS test, each rat was stereotaxicaily implanted with 17 gestational day rat fetal tissue obtained from the dorsal pons and containing the primordia of the LC or with tissue obtained from the neocortex or were sham-grafted. Subsequent to grafting, rats were subjected to 3 additional AGS tests. 53% (10/19) of 6-OHDA treated GEPRs showed a significant reduction in seizure severity following transplantation of fetal LC tissue. In contrast, only 20% (1/5) of GEPRs infused with saline rather than 6-OHDA showed, a reduction of seizure severity following fetal LC transplantation. NE content in the cortex and pons/medulla was decreased by 78% and 46% respectively following 6-OHDA microinfusion into the LC. Prominent grafts with numerous TH positive neurons and neurites were present within the third ventricle of grafted animals, while cortex grafts contained no TH immunostained structures. These findings suggest that the efficacy of fetal LC tissue to promote reductions in seizure severity in GEPRs is increased following depletion of central NE by microinfusion of 6-OHDA

The Edgewater Coolside process demonstration

The Edgewater Coolside process demonstration met the program objectives which were to determine Coolside SO[sub 2] removal performance, establish short-term process operability, and evaluate the economics of the process versus a limestone wet scrubber. On a flue gas produced from the combustion of 3% sulfur coal, the Coolside process achieved 70% SO[sub 2] removal using commercially-available hydrated lime as the sorbent. The operating conditions were Ca/S mol ratio 2.0, Na/Ca mol ratio 0.2, and 20[degree]F approach to adiabatic saturation temperature ([del]T). During tests using fresh plus recycle sorbent, the recycle sorbent exhibited significant capacity for additional SO[sub 2] removal. The longest steady state operation was eleven days at nominally Ca/S = 2, Na/Ca = 0.22, [del]T = 20--22[degree]F, and 70% SO[sub 2] removal. The operability results achieved during the demonstration indicate that with the recommended process modifications, which are discussed in the Coolside process economic analysis, the process could be designed as a reliable system for utility application. Based on the demonstration program, the Coolside process capital cost for a hypothetical commercial installation was minimized. The optimization consisted of a single, large humidifier, no spare air compressor, no isolation dampers, and a 15 day on-site hydrated lime storage. The levelized costs of the Coolside and the wet limestone scrubbing processes were compared. The Coolside process is generally economically competitive with wet scrubbing for coals containing up to 2.5% sulfur and plants under 350 MWe. Site-specific factors such as plant capacity factor, SO[sub 2] emission limit, remaining plant life, retrofit difficulty, and delivered sorbent cost affect the scrubber-Coolside process economic comparison

Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125 or 0.5 mg/infusion) both under a Fixed Ratio 1 and a Progressive Ratio schedule of reinforcement compared to wild type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showeda significantly lower drug intake compared to Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.Neuropsychopharmacology accepted article preview online, 26 August 2016. doi:10.1038/npp.2016.171

The hypothalamic RFamide, QRFP, increases feeding and locomotor activity:The role of Gpr103 and orexin receptors

Here we show that central administration of pyroglutamylated arginine-phenylamine-amide peptide (QRFP/26RFa) increases both food intake and locomotor activity, without any significant effect on energy expenditure, thermogenesis or reward. Germline knock out of either of the mouse QRFP receptor orthologs, Gpr103a and Gpr103b, did not produce a metabolic phenotype. However, both receptors are required for the effect of centrally administered QRFP to increase feeding and locomotor activity. As central injection of QRFP activated orexin/hypocretin neurons in the lateral hypothalamus, we compared the action of QRFP and orexin on behaviour. Both peptides increased arousal and locomotor activity. However, while orexin increased consummatory behaviour, QRFP also affected other appetitive behaviours. Furthermore, the feeding but not the locomotor response to QRFP, was blocked by co-administration of an orexin receptor 1 antagonist. These results suggest that QRFP agonism induces both appetitive and consummatory behaviour, but only the latter is dependent on orexin/hypocretin receptor signalling.</p