Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons.

To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinson's disease-like neurotoxicity, we used 1-methyl-4-phenylpyridinium (MPP) treatment (a model of Parkinson's disease). We show that MPP-induced neurotoxicity was dependent on ROS from neuronal NO synthase (nNOS) in nNOS-expressing PC12 cells (NPC12 cells) and rat cerebellar granule neurons (CGNs). Following MPP treatment, we found production of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a second messenger in the NO/ROS redox signaling pathway, in NPC12 cells and rat CGNs, that subsequently induced S-guanylation and activation of H-Ras.

Exposure to Electrophiles Impairs Reactive Persulfide-Dependent Redox Signaling in Neuronal Cells.

Electrophiles such as methylmercury (MeHg) affect cellular functions by covalent modification with endogenous thiols. Reactive persulfide species were recently reported to mediate antioxidant responses and redox signaling because of their strong nucleophilicity. In this study, we used MeHg as an environmental electrophile and found that exposure of cells to the exogenous electrophile elevated intracellular concentrations of the endogenous electrophilic molecule 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), accompanied by depletion of reactive persulfide species and 8-SH-cGMP which is a metabolite of 8-nitro-cGMP.

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice.

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure.

Purinergic P2Y receptors: Molecular diversity and implications for treatment of cardiovascular diseases.

Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes.

Purinergic P2Y receptors: A new therapeutic target of age-dependent hypertension.

Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility.

Distinct and Cooperative Functions for the -α, -β and -γ Clusters in Neuronal Survival and Axon Targeting.

The clustered () genes are divided into the αβ, and γ clusters. Gene-disruption analyses in mice have revealed the functions of the α and γ clusters. However, all Pcdh protein isoforms form combinatorial -hetero dimers and enter -homophilic interactions.

Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness.

Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship.

Processing Load Imposed by Line Breaks in English Temporal Wh-Questions.

Prosody plays an important role in online sentence processing both explicitly and implicitly. It has been shown that prosodically packaging together parts of a sentence that are interpreted together facilitates processing of the sentence. This applies not only to explicit prosody but also implicit prosody.

A Microsaccadic Account of Attentional Capture and Inhibition of Return in Posner Cueing.

Microsaccades exhibit systematic oscillations in direction after spatial cueing, and these oscillations correlate with facilitatory and inhibitory changes in behavioral performance in the same tasks. However, independent of cueing, facilitatory and inhibitory changes in visual sensitivity also arise pre-microsaccadically. Given such pre-microsaccadic modulation, an imperative question to ask becomes: how much of task performance in spatial cueing may be attributable to these peri-movement changes in visual sensitivity? To investigate this question, we adopted a theoretical approach.

The Brain Mechanisms Underlying the Perception of Pungent Taste of Capsaicin and the Subsequent Autonomic Responses.

In a human fMRI study, it has been demonstrated that tasting and ingesting capsaicin activate the ventral part of the middle and posterior short gyri (M/PSG) of the insula which is known as the primary gustatory area, suggesting that capsaicin is recognized as a taste. Tasting and digesting spicy foods containing capsaicin induce various physiological responses such as perspiration from face, salivation, and facilitation of cardiovascular activity, which are thought to be caused through viscero-visceral autonomic reflexes. However, this does not necessarily exclude the possibility of the involvement of higher-order sensory-motor integration between the M/PSG and anterior short gyrus (ASG) known as the autonomic region of the insula.

Multi-Dimensional Dynamics of Human Electromagnetic Brain Activity.

Magnetoencephalography (MEG) and electroencephalography (EEG) are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency), which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses.

Does heterogeneity of intracellular Ca[Formula: see text] dynamics underlie speed tuning of direction-selective responses in starburst amacrine cells?

The starburst amacrine cell (SAC) plays a fundamental role in retinal motion perception. In the vertebrate retina, SAC dendrites have been shown to be directionally selective in terms of their Ca[Formula: see text] responses for stimuli that move centrifugally from the soma. The mechanism by which SACs show Ca[Formula: see text] bias for centrifugal motion is yet to be determined with precision.

Comprehensive Behavioral Analysis of Male Ox1r (-/-) Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior.

Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system.

Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice.

Calcium (Ca(2+)) influx through voltage-gated Ca(2+) channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca(2+) signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits.

Differential age-related changes in N170 responses to upright faces, inverted faces, and eyes in Japanese children.

The main objectives of this study were to investigate the development of face perception in Japanese children, focusing on the changes in face processing strategies (holistic and/or configural vs. feature-based) that occur during childhood. To achieve this, we analyzed the face-related N170 component, evoked by upright face, inverted face, and eyes stimuli in 82 Japanese children aged between 8- and 13-years-old.

Nicotinamide adenine dinucleotide (NAD) may affect DNA methyltransferase 1 through regulation of BRCA1 in ovarian cancer.

Nicotinamide adenine dinucleotide (NAD) is a crucial molecule of energy production and signal transduction processes that have been linked to ovarian cancer development. Notably, emerging evidence has led to considerable interest in the role of DNA methyltransferase 1 (DNMT1) in the initiation and progression of ovarian cancer. However, dynamic crosstalk between NAD and DNMT1 is poorly understood.

Neuronal polarization in the developing cerebral cortex.

Cortical neurons consist of excitatory projection neurons and inhibitory GABAergic interneurons, whose connections construct highly organized neuronal circuits that control higher order information processing. Recent progress in live imaging has allowed us to examine how these neurons differentiate during development in vivo or in in vivo-like conditions. These analyses have revealed how the initial steps of polarization, in which neurons establish an axon, occur.

Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus.

Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging, and neurophysiological methods, such as magnetoencephalography and electroencephalography, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence.

Frequency-specific network topologies in the resting human brain.

A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both "communities" and "hubs" exist simultaneously in the brain's functional connectivity network (FCN), as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signal changes (0.

Brain-machine interface to control a prosthetic arm with monkey ECoGs during periodic movements.

Brain-machine interfaces (BMIs) are promising technologies for rehabilitation of upper limb functions in patients with severe paralysis. We previously developed a BMI prosthetic arm for a monkey implanted with electrocorticography (ECoG) electrodes, and trained it in a reaching task. The stability of the BMI prevented incorrect movements due to misclassification of ECoG patterns.

The role of GABA in the regulation of GnRH neurons.

Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA) has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA.

Neural networks involved in learning lexical-semantic and syntactic information in a second language.

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of language acquisition in a realistic learning environment. Japanese native speakers were trained in a miniature version of German prior to fMRI scanning. During scanning they listened to (1) familiar sentences, (2) sentences including a novel sentence structure, and (3) sentences containing a novel word while visual context provided referential information.

Neural adaptation to silence in the human auditory cortex: a magnetoencephalographic study.

Introduction: Previous studies demonstrated that a decrement in the N1m response, a major deflection in the auditory evoked response, with sound repetition was mainly caused by bottom-up driven neural refractory periods following brain activation due to sound stimulations. However, it currently remains unknown whether this decrement occurs with a repetition of silences, which do not induce refractoriness.

Methods: In the present study, we investigated decrements in N1m responses elicited by five repetitive silences in a continuous pure tone and by five repetitive pure tones in silence using magnetoencephalography.