Structurally Distinct Nurr1 Ligands Exhibit Different Pharmacological Characteristics in Regulating Inflammatory Responses of Microglial BV-2 Cells.

Nurr1 (NR4A2) is a member of nuclear receptor superfamily that regulates gene transcription in midbrain dopaminergic neurons and also inhibits nuclear factor-κB-mediated inflammatory responses in brain microglial cells. To date, various compounds have been reported to stimulate transcriptional activity of Nurr1 on neuronal genes, but their anti-inflammatory actions are poorly characterized. The present study examined the effects of three kinds of Nurr1 ligands, amodiaquine, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)-methane (C-DIM12) and 5-chloronaphthalen-1-amine (5-CNA), on inflammatory responses of microglial BV-2 cells.

Experimental Approaches Used to Investigate Voluntary Behavioral Thermoregulatory Responses.

A new behavioral test was developed to investigate the neural mechanisms of voluntary, behavioral thermoregulatory responses. The apparatus used in this test consisted of a thermostatic chamber that maintained the ambient temperature at a chosen level and two side-by-side floor plates that were placed in the thermostatic chamber and could be set to different temperatures. As the three temperatures, ambient temperature and two plate temperatures, can be controlled independently, we term this behavioral test the three-temperature (3 T) test.

Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38.

Aromatic (Ar)-turmerone is a bioactive component of turmeric oil obtained from . We recently identified a novel analog (A2) of ar-turmerone that protects dopaminergic neurons from toxic stimuli by activating nuclear factor erythroid 2-related factor 2 (Nrf2). D-cysteine increases Nrf2, leading to the activation of chaperone-mediated autophagy (CMA), a pathway in the autophagy-lysosome protein degradation system, in primary cultured cerebellar Purkinje cells.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice.

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice.

Evaluation of behavioural selection processes in conflict scenarios using a newly developed mouse behavioural paradigm.

Selecting an appropriate behaviour is critical for survival in conflict scenarios, wherein animals face both appetitive and aversive stimuli. Behavioural selection consists of multiple processes: (1) animals remain quiet in a safe place to avoid aversive stimuli (suspension), (2) once they decide to take risks to approach appetitive stimuli, they assess the risks (risk assessment), and (3) they act to reach the reward. However, most studies have not addressed these distinct behavioural processes separately.

Colletofragarone A2 Inhibits Cancer Cell Growth and Leads to the Degradation and Aggregation of Mutant p53.

Mutant p53 not only loses its original tumor suppressor function but also acquires new abilities regarding oncogenic progression. Therefore, the strategy of targeting mutant p53 has attracted attention for cancer therapy. We isolated colletofragarone A2 (CF) from the fungus sp.

Neurotensin orchestrates valence assignment in the amygdala.

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning. However, we do not yet understand how valence-specific information is routed to the BLA neurons with the appropriate downstream projections, nor do we understand how to reconcile the sub-second timescales of synaptic plasticity with the longer timescales separating the predictive cues from their outcomes.

Exposure to hot and cold environments activates neurons projecting from the paraventricular thalamic nucleus to brain regions related to approach and avoidance behaviors.

Although cool- and warm-seeking behaviors for behavioral thermoregulation are considered to be appetitive/approach and aversive/avoidance behaviors, the neuronal circuits mediating such behaviors remain to be elucidated. A growing body of evidence suggests that the paraventricular thalamic nucleus (PVT) is a key brain region in a neuronal circuit that mediates appetitive/approach and aversive/avoidance behaviors. In this study, to elucidate the neuronal circuits mediating behavioral thermoregulatory responses, we examined whether neuronal pathways from the PVT to the nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and central nucleus of the amygdala (CeA), which are brain regions implicated in mediating appetitive/approach and aversive/avoidance behaviors, are activated during exposure to hot (38°C) and cold (8°C) environments using c-Fos immunostaining and retrograde tracing.

Resolvin E1 Attenuates Chronic Pain-Induced Depression-Like Behavior in Mice: Possible Involvement of Chemerin Receptor ChemR23.

The antidepressant effect of eicosapentaenoic acid-derived bioactive lipid, resolvin E1 (RvE1), was examined in a murine model of chronic pain-induced depression using a tail suspension test. Because RvE1 reportedly possesses agonistic activity on a chemerin receptor ChemR23, we also examined the antidepressant effect of chemerin. Two weeks after surgery for unilateral spared nerve injury to prepare neuropathic pain model mice, immobility time was measured in a tail suspension test.

Resolvin D2 attenuates chronic pain-induced depression-like behavior in mice.

Aim: We previously demonstrated that intracerebroventricular injection of resolvin D2 (RvD2), a bioactive lipid mediator derived from docosahexaenoic acid, ameliorated depression-like behavior in lipopolysaccharide-induced and chronic mild stress-induced mouse models of depression. In the present study, we examined the antidepressant effect of RvD2 on chronic pain-induced depression-like behavior.

Methods: To prepare the neuropathic pain model, mice were subjected to surgery for unilateral spared nerve injury.

Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.

Background: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory.

GABAergic malfunction in the anterior cingulate cortex underlying maternal immune activation-induced social deficits.

Social deficits are one of the major symptoms of psychiatric disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, the underlying mechanism remains ill-defined. Here, we focused on the anterior cingulate cortex (ACC), a brain region that is related to social behaviors, of mice that received poly(I:C)-induced maternal immune activation.

Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23.

Rationale: Resolvins are bioactive lipid mediators that are generated from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). We recently demonstrated that the DHA-derived resolvins D1 and D2 exert antidepressant effects. However, whether the EPA-derived resolvins E1 (RvE1) and E2 (RvE2) produce antidepressant effects is not clear.

Emergence in extinction of enhanced and persistent responding to ambiguous aversive cues is associated with high MAOA activity in the prelimbic cortex.

There is a great deal of individual variability in the emotional outcomes of potentially traumatic events, and the underlying mechanisms are only beginning to be understood. In order to further our understanding of individual trajectories to trauma, its vulnerability and resilience, we adapted a model of fear expression to ambiguous vs perfect cues in adult male rats, and examined long-term fear extinction, 2, 3, and 50 days from acquisition. After the final conditioned fear test, mitochondrial enzyme monoamine oxidase A (MAOA) function was examined.

Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits.

Prevention of relapses is a major challenge in treating anxiety disorders. Fear reinstatement can cause relapse in spite of successful fear reduction through extinction-based exposure therapy. By utilising a contextual fear-conditioning task in mice, we found that reinstatement was accompanied by decreased c-Fos expression in the infralimbic cortex (IL) with reduction of synaptic input and enhanced c-Fos expression in the medial subdivision of the central nucleus of the amygdala (CeM).

Memory formation and retrieval of neuronal silencing in the auditory cortex.

Sensory stimuli not only activate specific populations of cortical neurons but can also silence other populations. However, it remains unclear whether neuronal silencing per se leads to memory formation and behavioral expression. Here we show that mice can report optogenetic inactivation of auditory neuron ensembles by exhibiting fear responses or seeking a reward.

Synaptic plasticity associated with a memory engram in the basolateral amygdala.

Synaptic plasticity is a cellular mechanism putatively underlying learning and memory. However, it is unclear whether learning induces synaptic modification globally or only in a subset of neurons in associated brain regions. In this study, we genetically identified neurons activated during contextual fear learning and separately recorded synaptic efficacy from recruited and nonrecruited neurons in the mouse basolateral amygdala (BLA).