Chronic activation of ß-adrenergic receptors leads to tissue water and electrolyte retention.

Beta-adrenergic receptors (ß-AR) are expressed on the membranes of various cell types and their activation affects body water balance by modulating renal sodium and water excretion, cardiovascular function and metabolic processes. However, ß-AR-associated body fluid imbalance has not been well characterised. In the present study, we hypothesized that chronic ß-AR stimulation increases electrolyte and water content at the tissue level. We evaluated the effects of isoproterenol, a non-selective ß-AR agonist, on electrolyte and water balance at the tissue level. Continuous isoproterenol administration for 14 days induced cardiac hypertrophy, associated with sodium-driven water retention in the heart, increased the total body sodium, potassium and water contents at the tissue level, and increased the water intake and blood pressure of the mice. There was greater urine output in response to the isoproterenol-induced body water retention. These isoproterenol-induced changes were reduced by propranolol, a non-selective beta-receptor inhibitor. Isoproterenol-treated mice even without excessive water intake had higher total body electrolyte and water contents, and this tissue water retention was associated with lower dry body mass, suggesting that ß-AR stimulation in the absence of excess water intake induces catabolism and water retention. These findings suggest that ß-AR activation induces tissue sodium and potassium retention, leading to body fluid retention, with or without excess water intake. This characterisation of ß-AR-induced electrolyte and fluid abnormalities improves our understanding of the pharmacological effects of ß-AR inhibitors. Significance Statement We have shown that chronic ß-AR stimulation causes cardiac hypertrophy associated with sodium-driven water retention in the heart and increases the accumulation of body sodium, potassium and water at the tissue level. This characterisation of the ß-AR-induced abnormalities in electrolyte and water balance at the tissue level improves our understanding of the roles of ß-AR in physiology and pathophysiology and the pharmacological effects of ß-AR inhibitors.

Transporters, Ion Channels, and Junctional Proteins in Choroid Plexus Epithelial Cells.

The choroid plexus (CP) plays significant roles in secreting cerebrospinal fluid (CSF) and forming circadian rhythms. A monolayer of epithelial cells with tight and adherens junctions of CP forms the blood-CSF barrier to control the movement of substances between the blood and ventricles, as microvessels in the stroma of CP have fenestrations in endothelial cells. CP epithelial cells are equipped with several kinds of transporters and ion channels to transport nutrient substances and secrete CSF. In addition, junctional components also contribute to CSF production as well as blood-CSF barrier formation. However, it remains unclear how junctional components as well as transporters and ion channels contribute to the pathogenesis of neurodegenerative disorders. In this manuscript, recent findings regarding the distribution and significance of transporters, ion channels, and junctional proteins in CP epithelial cells are introduced, and how changes in expression of their epithelial proteins contribute to the pathophysiology of brain disorders are reviewed.

E-Cadherin Is Expressed in Epithelial Cells of the Choroid Plexus in Human and Mouse Brains.

Evidence showing the functional significance of the choroid plexus is accumulating. Epithelial cells with tight and adherens junctions of the choroid plexus play important roles in cerebrospinal fluid production and circadian rhythm formation. Although specific types of cadherin expressed in adherens junctions of choroid plexus epithelium (CPE) have been examined, they remained uncertain. Recent mass spectrometry and immunolocalization analysis revealed that non-epithelial cadherins, P- and N-cadherins, are expressed in the lateral membrane of CPE, whereas E-cadherin expression has not been confirmed in CPE of humans or mice. In this study, we examined E-cadherin expression in CPE of mice and humans by RT-PCR, immunohistochemical-, and Western blotting analyses. We confirmed, by using RT-PCR analysis, the mRNA expression of E-cadherin in the choroid plexus of mice. The immunohistochemical expression of E-cadherin was noted in the lateral membrane of CPE of mice and humans. We further confirmed, in Western blotting, the specific immunoreactivity for E-cadherin. Immunohistochemically, the expression of E- and N-cadherins or vimentin was unevenly distributed in some CPE, whereas that of E- and P-cadherins or ß-catenin frequently co-existed in other CPE. These findings indicate that E-cadherin is expressed in the lateral membrane of CPE, possibly correlated with the expression of other cadherins and cytoplasmic proteins.

Enhanced structural connectivity within the motor loop in professional boxers prior to a match.

Professional boxers train to reduce their body mass before a match to refine their body movements. To test the hypothesis that the well-defined movements of boxers are represented within the motor loop (cortico-striatal circuit), we first elucidated the brain structure and functional connectivity specific to boxers and then investigated plasticity in relation to boxing matches. We recruited 21 male boxers 1 month before a match (Time1) and compared them to 22 age-, sex-, and body mass index (BMI)-matched controls. Boxers were longitudinally followed up within 1 week prior to the match (Time2) and 1 month after the match (Time3). The BMIs of boxers significantly decreased at Time2 compared with those at Time1 and Time3. Compared to controls, boxers presented significantly higher gray matter volume in the left putamen, a critical region representing motor skill training. Boxers presented significantly higher functional connectivity than controls between the left primary motor cortex (M1) and left putamen, which is an essential region for establishing well-defined movements. Boxers also showed significantly higher structural connectivity in the same region within the motor loop from Time1 to Time2 than during other periods, which may represent the refined movements of their body induced by training for the match.

Exploring the Neural Correlates in Adopting a Realistic View: A Neural Structural and Functional Connectivity Study With Female Nurses.

Empathizing leads to positive and negative consequences. To avoid empathy-induced distress, adopting a realistic view (dealing with a situation practically and efficiently independent of one's emotional state) is important. We hypothesized that empathy-demanding professions (e.g., nursing) may require individuals to adopt a realistic view, which may demonstrate modulated neural structure and functional connectivity. We confirmed that female nurses showed a higher tendency, compared to controls, to adopt a realistic view, using the Fantasy subscale of the Interpersonal Reactivity Index (IRI; inverse scale of the realistic view). We then employed voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) to explore the neural underpinnings related to realistic view adoption. Nurses exhibited significantly lower gray-matter volume (GMV) in the right striatum. In multiple regression analysis, only the Fantasy subscale score showed a significant positive correlation with GMV within the striatum cluster. Moreover, nurses exhibited lower functional connectivity between the right striatum and the right lateral prefrontal cortex (PFC), representing emotional regulation. These findings show that structural differences in the striatum correlated with the realistic view. Furthermore, lower functional connectivity between the striatum and lateral PFC suggests that nurses may use efficient coping strategies that may lessen the recruitment of effortful emotional regulation.

Prosocial behavior toward estranged persons modulates the interaction between midline cortical structures and the reward system.

Good reputation enhances positive self-image, which motivates prosocial behavior, a phenomenon known as indirect reciprocity. Thus, good reputation should promote prosocial behavior toward estranged people to whom affective responses leading to direct reciprocity are suppressed. We predicted that such behaviors involve an interrelationship between self-image, processed in the medial prefrontal cortex (mPFC) and precuneus, and social reward, processed in the reward system. To test our hypothesis, we performed fMRI on 21 participants during a virtual ball-toss game after subjects formed negative impressions (estrangement) or neutral impressions of other players. During some blocks of the game, the other players did not receive tosses, and participants could increase tosses to them (i.e. engage in prosocial behavior). Participants significantly increased tosses to all isolated players; therefore, prosocial behavior occurred irrespective of estrangement. Prosocial behavior toward estranged players enhanced positive self-image and increased activation of the anterior mPFC and precuneus. The precuneus exhibited enhanced functional connectivity with the striatum. Thus, a positive self-image, represented by an interaction between the midline cortical structures and striatum, plays key roles in prosocial behavior toward estranged people.

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. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68). Furthermore, we also conducted a voxel-based morphometry study of the effects of being in a romantic relationship (N = 113). Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

[Anesthesia and Consciousness].

The mechanism of consciousness and loss of conciousness by general anesthetics are crucial issue for the anesthesiologists. Recent non-invasive brain-imaging technology brings about light to various our emotions and sensations in human brain; however, neural correlate of consciousness is not yet still elucidated. The concept "the seat of the consciousness (is in the subcortical nuclei)" is now completely denied, but instead the consciousness is based on the idea that connectivity and communications across cortical and thalamocortical networks. Anesthetics and sleep disrupt the networks that encompass complexity and integration. The compatibility between complexity and integration is the key feature of the consciousness, which is represented by complex, extensive, communicative and integrative electroencephalograph currents evoked by transcranial magnetic stimulation, provoking a single unified conscious experience in us, humans.

Brain morphological alternation in chronic pain patients with neuropathic characteristics.

BACKGROUND: Neuropathic characteristics are highly involved in the development of chronic pain both physically and psychologically. However, little is known about the relationship between neuropathic characteristics and brain morphological alteration. OBJECTIVES: The aim of this study is to investigate the mechanisms of chronic pain development by examining the above-mentioned relationships by voxel-based morphometry in patients with chronic pain. METHODS: First, we assessed neuropathic characteristics using the painDETECT Questionnaire in 12 chronic pain patients. Second, to assess the gray matter volume changes by voxel-based morphometry, we conducted magnetic resonance imaging of the brain. We applied multiregression analysis of these two assessment methods. RESULTS: There were significant positive correlations between painDETECT Questionnaire scores and the gray matter volume in the bilateral anterior cingulate cortex and right posterior cingulate cortex. CONCLUSIONS: Our findings suggest that neuropathic characteristics strongly affect the brain regions related to modulation of pain in patients with chronic pain and, therefore, contribute to the severity of chronic pain.

Dehydration enhances pain-evoked activation in the human brain compared with rehydration.

BACKGROUND: Negative effects of dehydration on the human brain and cognitive function have been reported. In this study, we examined the effects of dehydration on pain thresholds and cortical activations in response to pain, compared with rehydration with an oral rehydration solution (ORS) by functional magnetic resonance imaging. METHODS: Five healthy adult men were subjected to dehydration and rehydration on 2 different days. The condition on the first day was randomly assigned to each subject. They completed a 40-minute exercise protocol using a walking machine after 12 hours of fasting under both conditions. For rehydration, the subjects consumed up to 3000 mL ORS starting from the night before the test day. After exercise, a painful stimulus (cold pressor test) was applied to the subjects' medial forearm in a magnetic resonance imaging scanning gantry, and pain-evoked brain activation was analyzed. RESULTS: On the rehydration day, each of the subjects consumed an average of 2040 mL (range; 1800-2500 mL) ORS. Physiological data revealed that subjects when dehydrated lost more weight from exercise than subjects when rehydrated had a larger heart rate increase, a higher tympanic temperature, and a higher urine osmolality. Subjective data revealed that the subjects reported significantly stronger thirst while dehydrated than while rehydrated with ORS, although the levels of hunger and anxiety and mood did not significantly differ between conditions. The cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, and thalamus. Such activations in the dehydrated subjects were greater than those in the rehydrated subjects in terms of peak and cluster, accompanied by a decrease in pain threshold (P = 0.001). CONCLUSION: Our findings suggest that dehydration brings about increased brain activity related to painful stimuli together with enhanced thirst, whereas rehydration with ORS alleviates thirst and decreases brain activity related to painful stimuli.

Sweet taste-induced analgesia: an fMRI study.

We investigated the brain activation associated with sweet taste-induced analgesia by 3-T functional magnetic resonance imaging, the mechanism of which is considered to involve the central nervous system. After 12 healthy individuals ingested tasteless gelatin (nonsweet condition) or sweet glucose (sweet condition) in a magnetic resonance imaging scanning gantry, the cold pressor test was applied to their medial forearm. Under both conditions, the cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, posterior parietal cortex, and thalamus, although such activations under the sweet condition weakened with pain threshold increase, compared with those under the nonsweet condition. Together with emotional changes in pain appraisal, our findings provide objective representation of sweet taste-induced analgesia in the human brain.

[A pitfall of AirWay Scope--an experience of distinctive airway edema after palatal laceration caused by irWay Scope].

Pentax AirWay Scope (AWS) is a new videolaryngoscope which allows indirect visualization of the vocal cords and provides a better laryngeal view compared with the conventional Macintosh laryngoscope. We report a female patient who developed distinctive upper airway edema after palatal laceration at the time of insertion of the AWS. She was scheduled for tympanoplasty. After anesthesia induction, there was technical difficulties in tracheal intubation with Macintosh laryngoscope (her Cormack grade was rated as 3), and we used the AWS, but could not obtain an appropriate view on the monitor. When the device was removed, we detected bleeding derived from the right palatal laceration. Following the aspiration of the blood, we could barely achieve tracheal intubation with a flexible fiberscope without hypoxemic episode. The upper airway including the arytenoid and vocal cords were distinctively edematous after the operation. Then, the tracheal tube was left for three days after the operation, to secure the airway until the reduction of airway edema. On the postoperative day 4, following the fibroscopic confirmation that the airway edema was reduced, the patient was extubated successfully. AWS should be used more carefully, especially at the time of insertion along the palate.

Inner experience of pain: imagination of pain while viewing images showing painful events forms subjective pain representation in human brain.

Pain is an unpleasant sensation, and at the same time, it is always subjective and affective. Ten healthy subjects viewed 3 counterbalanced blocks of images from the International Affective Picture System: images showing painful events and those evoking emotions of fear and rest. They were instructed to imagine pain in their own body while viewing each image showing a painful event (the imagination of pain). Using functional magnetic resonance imaging, we compared cerebral hemodynamic responses during the imagination of pain with those to emotions of fear and rest. The results show that the imagination of pain is associated with increased activity in several brain regions involved in the pain-related neural network, notably the anterior cingulate cortex (ACC), right anterior insula, cerebellum, posterior parietal cortex, and secondary somatosensory cortex region, whereas increased activity in the ACC and amygdala is associated with the viewing of images evoking fear. Our results indicate that the imagination of pain even without physical injury engages the cortical representations of the pain-related neural network more specifically than emotions of fear and rest; it also engages the common representation (i.e., in ACC) between the imagination of pain and the emotion of fear.

Somatotopy in human primary somatosensory cortex in pain system.

BACKGROUND: Compared with somatotopical organization (somatotopy) in the postcentral gyrus in the tactile system, somatotopy in the pain system is not well understood. The aim of this study is to elucidate whether there is somatotopy in the human pain system. METHODS: To elucidate the somatotopy of nociceptive neurons in the postcentral gyrus, the authors recorded pain-evoked cortical responses to noxious intraepidermal electrical stimulation applied to the left hand and left foot in 11 male subjects, using magnetoencephalography. RESULTS: Brief painful stimuli evoked sustained cortical activity in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side and in the secondary somatosensory cortex in both hemispheres. In SI, representations of the hand and foot were distinctly separated, with a more medial and posterior location for the foot, whereas no significant difference was found in the locations for the secondary somatosensory cortex dipole. The SI arrangement along the central sulcus was compatible with the homunculus revealed by Penfield using direct cortical stimulation during surgery. CONCLUSIONS: The human pain system contains a somatotopical representation in SI but with less somatotopical organization in the secondary somatosensory cortex. The current results provide supporting evidence of SI involvement in human pain perception and suggest that human SI subserves the localization of the stimulated site in nociceptive processing.