PKMζ has been proposed to be essential for maintenance of long-term potentiation (LTP) and long-term memory (LTM). However, recent data from PKMζ-knockout mice has called this role into question. Instead, the other atypical isoform, protein kinase C iota/lambda (PKCι/λ), has emerged as a potential alternative player. Therefore, the nature of the "memory molecule" maintaining learned information remains uncertain. Here, we report knockdown (KD) of PKCι/λ and PKMζ in the dorsal hippocampus and find deficits in early expression and late maintenance, respectively, during both LTP and hippocampus-dependent LTM. Sequential increases in the active form of PKCι/λ and PKMζ are detected during LTP or fear conditioning. Importantly, PKMζ, but not PKCι/λ, KD disrupts previously established LTM. Thus, PKCι/λ and PKMζ have distinct functions in LTP and memory, with PKMζ playing a specific role in memory maintenance. This relaying pattern may represent a precise molecular mechanism by which atypical PKCs regulate the different stages of memory.

Background/Aims: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke. Methods: We demonstrate that dose-dependent geniposide significantly decreased the infarct volume in tMCAO models. Results: A medium level of geniposide improved anti-apoptotic functions and inhibited BBB leakage/haemorrhage via elevating GluN2A-containing NMDAR expression in tMCAO rats. Importantly, these effects could be eliminated by co-treatment of geniposide with the GluN2A antagonist NVP but not the GluN2B inhibitor ifenprodil. Moreover, geniposide’s protection was due to the enhancement of GluN2A-dependent survival signals, including pAKT, pERK and PSD-95. Conclusion: The results suggest that geniposide protects neurons against post-ischaemic neurovascular injury through the activation of GluN2A/AKT/ERK pathways. As a very promising natural agent, geniposide may be a future therapeutic for stroke patients.

Melatonin (N-acetyl-5-methoxytryptamine), a naturally occurring small molecule, can protect plants against abiotic stress after exogenous treatmenting with it. It is not known if melatonin homologs, such as 5-methoxytryptamine and 5-methoxyindole, that are easy and more cost-effective to synthesize can stimulate the plant immune system in the same manner as melatonin. In the present study, we assessed the biological activity of the melatonin homologs, 5-methoxytryptamin and 5-methoxyindole. The results showed that melatonin and its homologs all induced disease resistance against Phytophthora nicotianae in Nicotiana benthamiana plants. The application of all three compounds also induced stomatal closure and the production of reactive oxygen species. Gene expression analysis indicated that the expression of genes involved in hydrogen peroxide (H2O2), nitric oxide (NO) production, and salicylic acid (SA) biosynthesis was significantly upregulated by all three compounds. Four homologs of the melatonin receptors were identified by blasting search with the phytomelatonin receptor in Arabidopsis. Molecular docking studies were also used to identify four putative melatonin receptors in N. benthamiana. Further experimentation revealed that silencing of the melatonin receptors trP47363 and trP13076 in N. benthamiana compromised the induction of stomatal closure, PR-1a gene expression and SA accumulation by all three compounds. Collectively, our data indicate that the induction of defense responses in N. benthamiana by melatonin, 5-methoxytryptamine, and 5-methoxyindole involves the melatonin receptors trP47363 and trP13076.