2-[4-(4,5-Dihydro-1H-imidazol-2-yl)phen­yl]-4,5-dihydro-1H-imidazol-3-ium 4-amino­benzoate

In the cation of the title compound, C12H15N4 +·C7H6NO2 −, the benzene ring makes dihedral angles of 30.51 (9) and 25.64 (9)° with the imidazole and imidazolinium rings, respectively. In the crystal, inter­molecular N—H⋯O and N—H⋯N hydrogen-bonding inter­actions link the mol­ecules into a three-dimensional network

Cleavage of lamin-like proteins in in vivo and in vitro apoptosis of tobacco protoplasts induced by heat shock

AbstractApoptosis in heat shock-treated tobacco protoplasts was evidenced by DNA fragmentation, flow cytometric analysis and activation of caspase 3-like protease. Furthermore, an in vitro apoptosis system was established which reproduced the apoptotic events. Western blotting analysis using an antibody against lamin A and C showed that in both in vivo and in vitro systems lamin-like proteins were cleaved into a 35-kDa fragment, and that lamin-like protein degradation precedes DNA fragmentation. Moreover, we found a 22.8-fold increase in caspase 6-like activity in cytosol of heat-treated protoplasts as compared with the control

Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex

Long-term potentiation (LTP) in the anterior cingulate cortex (ACC) is believed to be critical for higher brain functions including emotion, learning, memory and chronic pain. N-methyl-D-aspartate (NMDA) receptor-dependent LTP is well studied and is thought to be important for learning and memory in mammalian brains. As the downstream target of NMDA receptors, the extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) cascade has been extensively studied for its involvement in synaptic plasticity, learning and memory in hippocampus. By contrast, the role of ERK in cingulate LTP has not been investigated. In this study, we examined whether LTP in ACC requires the activation of ERK. We found that P42/P44 MAPK inhibitors, PD98059 and U0126, suppressed the induction of cingulate LTP that was induced by presynaptic stimulation with postsynaptic depolarization (the pairing protocol). We also showed that cingulate LTP induced by two other different protocols was also blocked by PD98059. Moreover, we found that these two inhibitors had no effect on the maintenance of cingulate LTP. Inhibitors of c-Jun N-terminal kinase (JNK) and p38, other members of MAPK family, SP600125 and SB203850, suppressed the induction of cingulate LTP generated by the pairing protocol. Thus, our study suggests that the MAPK signaling pathway is involved in the induction of cingulate LTP and plays a critical role in physiological conditions

Induction- and conditioning-protocol dependent involvement of NR2B-containing NMDA receptors in synaptic potentiation and contextual fear memory in the hippocampal CA1 region of rats

Long-term potentiation (LTP) in the hippocampal CA1 region requires the activation of N-methyl-D-aspartate receptors (NMDARs). Studies using genetic and pharmacological approaches have reported inconsistent results of the requirement of NR2B-containing NMDARs in LTP in the CA1 region. Pharmacological studies showed that NR2B-containing NMDARs are not required for LTP, while genetic studies reported that over-expression of NR2B-NMDARs enhances LTP and hippocampus-dependent memory. Here, we provide evidence showing that the functional role of NR2B-NMDARs in hippocampal LTP and memory depends on LTP-inducing and behavior-conditioning protocols. Inhibition of NR2B-NMDARs with the NR2B selective antagonist ifenprodil or Ro25-6981 suppressed LTP induced by spike-timing protocol, with no impact on LTP induced by pairing protocol or two-train high-frequency stimulation (HFS) protocol. Inhibition of NR2B-NMDARs did not affect the late phase LTP induced by four-train HFS. Ca2+ imaging showed that there was difference in kinetics of intracellular Ca2+ signals induced by spiking-timing and pairing protocols. Pre-training intra-CA1 infusion of ifenprodil or Ro25-6981 impaired the contextual fear memory induced by five CS-US pairings, with no effect on the memory induced by one CS-US pairing

2,2′-(p-Phenyl­ene)bis­(4,5-dihydro-1H-imidazol-3-ium) bis­(3-nitro­benzoate)

In the title compound, C12H16N4 +·2C7H4NO4 −, the complete 2,2′-(p-phenyl­ene)bis­(4,5-dihydro-1H-imidazol-3-ium) (bib) dication is generated by crystallographic inversion symmetry. The bib cations reside on crystallographic inversion centers, which coincide with the centroids of the respective benzene rings. In the cation, the imidazole ring adopts an envelop conformation with the flap atom displaced by 0.082 (3) Å from the plane through the other ring atoms. In the crystal, the cations and anions are linked through inter­molecular N—H⋯O hydrogen bonds, forming chains running along the a axis. C—H⋯O inter­actions also occur. Weak π–π contacts between the imidazole rings of bib and between the benzene rings of NB [centroid–centroid distances = 3.501 (1) and 3.281 (2) Å, respectively] may further stabilize the structure

Characterization of intracortical synaptic connections in the mouse anterior cingulate cortex using dual patch clamp recording

The anterior cingulate cortex (ACC) is involved in sensory, cognitive, and executive functions. Studies of synaptic transmission and plasticity in the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions. Previous anatomic studies suggest complex local interactions among neurons within the ACC. However, there is a lack of functional studies of such synaptic connections between ACC neurons. In the present study, we characterized the neuronal connections in the superficial layers (I-III) of the mouse ACC using dual whole-cell patch clamp recording technique. Four types of synaptic connections were observed, which are from a pyramidal neuron to a pyramidal neuron, from a pyramidal neuron to an interneuron, from an interneuron to a pyramidal neuron and from an interneuron to an interneuron. These connections exist among neurons in layer II/III or between neurons located layer I and II/III, respectively. Moreover, reciprocal connections exist in all four types of paired neurons. Our results provide the first key evidence of functional excitatory and inhibitory connections in the ACC

Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex

NMDA receptors (NMDARs) are involved in excitatory synaptic transmission and plasticity associated with a variety of brain functions, from memory formation to chronic pain. Subunit-selective antagonists for NMDARs provide powerful tools to dissect NMDAR functions in neuronal activities. Recently developed antagonist for NR2A-containing receptors, NVP-AAM007, triggered debates on its selectivity and involvement of the NMDAR subunits in bi-directional synaptic plasticity. Here, we re-examined the pharmacological properties of NMDARs in the anterior cingulate cortex (ACC) using NVP-AAM007 as well as ifenprodil, a selective antagonist for NR2B-containing NMDARs. By alternating sequence of drug application and examining different concentrations of NVP-AAM007, we found that the presence of NVP-AAM007 did not significantly affect the effect of ifenprodil on NMDAR-mediated EPSCs. These results suggest that NVP-AAM007 shows great preference for NR2A subunit and could be used as a selective antagonist for NR2A-containing NMDARs in the ACC