Search

Nicotine exerts its reinforcing actions by activating nicotinic acetylcholine receptors (nAChRs), but the detailed mechanisms remain unclear. Nicotine releases 3, 4-dihydroxyphenylalanine (DOPA), a neurotransmitter candidate in the central nervous system. Here, we investigated the distribution of GPR143, a receptor of DOPA, and nAChR subunits in the nigrostriatal and mesolimbic regions. We found GPR143 mRNA-positive cells in the striatum and nucleus accumbens. Some of them were surrounded by tyrosine hydroxylase (TH)-immunoreactive fibers. There were some GPR143 mRNA-positive cells coexpressing TH, and nAChR subunit α4 or α7 in the substantia nigra and ventral tegmental area. These findings suggest that DOPA-GPR143 signaling may be involved in the nicotine action in the nigrostriatal and mesolimbic dopaminergic systems.

Neurogenesis occurs in the hippocampus throughout life and is implicated in various physiological brain functions such as memory encoding and mood regulation. L-3,4-dihydroxyphenylalanine (L-DOPA) has long been believed to be an inert precursor of dopamine. Here, we show that L-DOPA and its receptor, GPR143, the gene product of ocular albinism 1, regulate neurogenesis in the dentate gyrus (DG) in a dopamine-independent manner. L-DOPA at concentrations far lower than that of dopamine promoted proliferation of neural stem and progenitor cells in wild-type mice under the inhibition of its conversion to dopamine; this effect was abolished in GPR143 gene-deficient (Gpr143−/y) mice. Hippocampal neurogenesis decreased during development and adulthood, and exacerbated depression-like behavior was observed in adult Gpr143−/y mice. Replenishment of GPR143 in the DG attenuated the impaired neurogenesis and depression-like behavior. Our findings suggest that L-DOPA through GPR143 modulates hippocampal neurogenesis, thereby playing a role in mood regulation in the hippocampus.

Kiwifruit exhibit a peculiar ripening pattern, as extensive softening is known to occur in the absence of any detectable ethylene. We previously demonstrated that this softening is regulated by low temperature independent of ethylene. However, there are no reports that provide comparisons of the ripening patterns among different kiwifruit cultivars at various storage temperatures. The purpose of this study was to compare the ripening responses and associated gene expression in ‘Sanuki Gold’ (Actinidia chinensis var. chinensis) and ‘Hayward’ ((Actinidia chinensis var. deliciosa) fruit, two kiwifruit cultivars differing in on–vine maturity dates and postharvest storability, during storage at 5 °C, 10 °C, 15 °C and 22 °C. Fruit softening, soluble solids concentration (SSC) increase and reduction of titratable acidity (TA) occurred in the absence of any detectable ethylene, and treatment with an ethylene inhibitor 1–methylcyclopropene (1–MCP) failed to suppress the changes, suggesting that they were independent of ethylene. ‘Sanuki Gold’ fruit showed a higher sensitivity to low temperature supported by accelerated fruit softening and TA reduction, and induction of several genes such as AcACO3, AcXET2, AcPG, AcEXP1, AcPMEi, AcGA2ox1, AcMADS2, AcNAC5 and AcbZIP2 at 5 °C, 10 °C and 15 °C within 28 d. By contrast, ‘Hayward’ fruit exhibited a lower sensitivity to low temperature as accelerated softening, TA reduction and induction of most ripening–associated genes were recorded only at 5 °C and 10 °C. These differences in sensitivity to low temperature, between ‘Sanuki Gold’ and ‘Hayward’ fruit, would account for the dissimilarities observed in on–vine maturity dates and postharvest storability.

Kiwifruit is considered a climacteric fruit since exogenous ethylene induces ripening-associated changes. However, we previously reported that low temperature modulated ripening in kiwifruit since ripening occurred faster during storage at 5°C compared to 20°C, in the absence of any detectable ethylene. It is therefore not clear which temperature is suitable for long-term storage of kiwifruit. The purpose of this study was to determine the optimum temperature for long-term storage, and analysis of ripening-related genes in 'Rainbow Red' kiwifruit. Kiwifruit were harvested at commercial maturity, and stored at either 0, 2, 5 or 22°C in ethylene-free chambers. During storage, incidence of fruit deterioration and changes in fruit firmness, soluble solids concentration (SSC) and titratable acidity (TA) were monitored at 4-week intervals. Real-time PCR was also conducted to analyze the changes in expression of selected ripening-related genes. Incidence of fruit fast senescence and deterioration was high at 22°C, so kiwifruit could only be stored for a maximum of 8 weeks. Nevertheless, healthy fruit at 22°C remained firm and maintained high TA for 8 weeks. The incidence of ethylene-producing fruit, and consequent fast senescence, was greatly reduced at 5°C, while it was completely suppressed at 0 and 2°C. Fruit at 5°C decreased in firmness and TA faster, attaining eating-ripe quality within 8 weeks. At 2°C, fruit decreased in firmness and TA gradually, achieving eating-ripe quality after 12 weeks. Conversely, fruit at 0°C maintained higher firmness and TA, and did not attain eating-ripe quality even after 12 weeks. SSC increased at all storage temperatures, although the lowest levels were observed in fruit at 0°C. Real-Time PCR analysis revealed that cell-wall-modifying genes (AcPG, AcPL2, AcEXP1 and AcXET2) and carbohydrate-metabolism-associated genes (Acβ-AMY1 and Acβ-AMY2) were markedly induced in fruit at 5°C. Overall, these results indicate that 0°C is the suitable temperature for long-term storage of kiwifruit, while 2°C is suitable for medium-term storage. For short-term storage, 5°C can be recommended.

l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective therapeutic agent for Parkinson's disease (PD). l-DOPA is traditionally believed to be an inert amino acid that exerts actions and effectiveness in PD through its conversion to dopamine. In contrast to this generally accepted idea, l-DOPA is proposed to be a neurotransmitter. Recently, GPR143 (OA1), the gene product of ocular albinism 1 was identified as a receptor candidate for l-DOPA. GPR143 is widely expressed in the central and peripheral nervous system. GPR143 immunoreactivity was colocalized with phosphorylated α-synuclein in Lewy bodies in PD brains. GPR143 may contribute to the therapeutic effectiveness of l-DOPA and might be related to pathogenesis of PD.

l-3,4-dihydroxyphenylalanine (l-DOPA) is a candidate neurotransmitter. l-DOPA is released by nicotine through nicotinic receptors. Recently, G-protein coupled receptor GPR143, was identified as a receptor for l-DOPA. In this study, genetic association studies between GPR143 genetic polymorphisms and smoking behaviors revealed that the single-nucleotide polymorphism rs6640499, in the GPR143 gene, was associated with traits of smoking behaviors in Japanese individuals. In Gpr143 gene-deficient mice, nicotine-induced hypolocomotion and rewarding effect were attenuated compared to those in wild-type mice. Our findings suggest the involvement of GPR143 in the smoking behaviors.

Hyperthermia-induced febrile seizures (FSs) are the most common seizures during childhood, and prolonged complex FSs can result in the development of epilepsy. Currently, GABA

Hyperthermia-induced febrile seizures (FSs) are the most common seizures during childhood, and prolonged complex FSs can result in the development of epilepsy. Currently, GABAAreceptor modulators such as benzodiazepines and barbiturates are used as medications for FSs with the aim of enhancing GABA-mediated inhibition of neuronal activity. However, it is still up for debate whether these enhancers of GABAergic neurotransmission could depolarize immature neurons with relatively higher levels of the intracellular Cl−in the developing brain during FSs. Here, we performed simultaneous video-local field potential monitoring to determine whether benzodiazepines and barbiturates affect the phenotypes of FSs in postnatal day (P)11 and P14 mice. We found that low-dose administration of diazepam decreased the incidence of clonic seizures at P11. We also found that high-dose administration of diazepam and pentobarbital exacerbated the behavioral and electrophysiological phenotypes of the induction phase of experimental FSs at P11 but not at P14. We further found that the deteriorated phenotypes at P11 were suppressed when Na+K+2Cl−cotransporter isoform 1 (NKCC1), which mediates Cl−influx, was blocked by treatment with the diuretic bumetanide. Though our findings do not exclude the involvement of sedation effect of high-dose GABAAreceptor modulators in worsening experimental FSs at P11, pharmacological enhancement of GABAergic signaling could aggravate seizure activity in the early phase of FSs.

The oxidative decarboxylation reactions of arylacetic acids to arylcarbinols were compared for Mn(III) acetate, Ce(IV) ammonium nitrate and a combination reagent of Co(III) acetate-Cu(II) acetate. The reaction with Mn(III)acetate in acetic acid gave the corresponding arylcarbinyl acetate usually in good yield. The reaction was particularly easy when the substrate carried an electron-donating group at the para position of the aromatic ring, or when the acid was secondary or tertiary. In contrast, the product generated with the other reagents was either a mixture containing over-oxidation products or products formed via a different route.