Cell-type-specific representation of spatial context in the rat prefrontal cortex.

The ability to represent one's own position in relation to cues, goals, or threats is crucial to successful goal-directed behavior. Using optotagging in knock-in rats expressing Cre recombinase in parvalbumin (PV) neurons (PV-Cre rats), we demonstrate cell-type-specific encoding of spatial and movement variables in the medial prefrontal cortex (mPFC) during goal-directed reward seeking. Single neurons encoded the conjunction of the animal's spatial position and the run direction, referred to as the spatial context. The spatial context was most prominently represented by the inhibitory PV interneurons. Movement toward the reward was signified by increased local field potential (LFP) oscillations in the gamma band but this LFP signature was not related to the spatial information in the neuronal firing. The results highlight how spatial information is incorporated into cognitive operations in the mPFC. The presented PV-Cre line opens the door for expanded research approaches in rats.

Exploring Variations in Sleep Perception: Comparative Study of Chatbot Sleep Logs and Fitbit Sleep Data.

BACKGROUND: Patient-generated health data are important in the management of several diseases. Although there are limitations, information can be obtained using a wearable device and time-related information such as exercise time or sleep time can also be obtained. Fitbits can be used to acquire sleep onset, sleep offset, total sleep time (TST), and wakefulness after sleep onset (WASO) data, although there are limitations regarding the depth of sleep and satisfaction; therefore, the patient's subjective response is still important information that cannot be replaced by wearable devices. OBJECTIVE: To effectively use patient-generated health data related to time such as sleep, it is first necessary to understand the characteristics of the time response recorded by the user. Therefore, the aim of this study was to analyze the characteristics of individuals' time perception in comparison with wearable data. METHODS: Sleep data were acquired for 2 weeks using a Fitbit. Participants' sleep records were collected daily through chatbot conversations while wearing the Fitbit, and the two sets of data were statistically compared. RESULTS: In total, 736 people aged 30-59 years were recruited for this study, and the sleep data of 543 people who wore a Fitbit and responded to the chatbot for more than 7 days on the same day were analyzed. Research participants tended to respond to sleep-related times on the hour or in 30-minute increments, and each participant responded within the range of 60-90 minutes from the value measured by the Fitbit. On average for all participants, the chat responses and the Fitbit data were similar within a difference of approximately 15 minutes. Regarding sleep onset, the participant response was 8 minutes and 39 seconds (SD 58 minutes) later than that of the Fitbit data, whereas with respect to sleep offset, the response was 5 minutes and 38 seconds (SD 57 minutes) earlier. The participants' actual sleep time (AST) indicated in the chat was similar to that obtained by subtracting the WASO from the TST measured by the Fitbit. The AST was 13 minutes and 39 seconds (SD 87 minutes) longer than the time WASO was subtracted from the Fitbit TST. On days when the participants reported good sleep, they responded 19 (SD 90) minutes longer on the AST than the Fitbit data. However, for each sleep event, the probability that the participant's AST was within ±30 and ±60 minutes of the Fitbit TST-WASO was 50.7% and 74.3%, respectively. CONCLUSIONS: The chatbot sleep response and Fitbit measured time were similar on average and the study participants had a slight tendency to perceive a relatively long sleep time if the quality of sleep was self-reported as good. However, on a participant-by-participant basis, it was difficult to predict participants' sleep duration responses with Fitbit data. Individual variations in sleep time perception significantly affect patient responses related to sleep, revealing the limitations of objective measures obtained through wearable devices.

Esr1+ hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns. We found that genetically defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors, such as estrogen receptor 1-expressing (Esr1+) LHA-LHb neurons induce aversion, whereas neuropeptide Y-expressing (Npy+) LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive signals in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

Partial sleep restriction-induced changes in stress, quality of life, and lipid metabolism in relation to cold hypersensitivity: A before-and-after intervention study.

Sleep disturbances are associated with cold hypersensitivity (CH) and characterized by excessive cold sensation in specific body parts and cold thermal discomfort. This study investigated the effects of short-term sleep restriction followed by a recovery phase on subjective health status, inflammation, and lipid metabolism in different types of CH. A total of 118 healthy adults aged 35 to 44 years without sleep disturbances were enrolled. Participants underwent 4-hour sleep restrictions per day for 3 days at a hospital and then returned to their daily lives for 4 days of rest. CH was assessed using a structured questionnaire with eight characteristic symptoms. A questionnaire and blood tests were administered baseline, after sleep restriction, and follow-up to assess cortisol, lipid profiles, and self-reported stress and quality of life (QOL). Participants were divided into CH (44.1%) and non-CH (55.9%) groups. The CH group showed increased stress, impaired QOL, and decreased low-density lipoprotein-cholesterol (LDL-C) levels compared to the non-CH group after sleep restriction. The variance for QOL (effect size = 0.07), subjective stress (effect size = 0.053), and LDL-C (effect size = 0.029) among time points depended on the group. Short-term sleep restriction was associated with deterioration of subjective health and reduced lipid metabolism; such changes were more evident in the CH group. Our findings suggest the need to consider an individual's CH status to assess the clinical risk associated with insufficient sleep.

Weight Control Registry Using Korean Medicine: A Protocol for a Prospective Registry Study.

Lifestyle and physical characteristics affect body weight, and understanding these factors improves the precision of weight loss treatment. Many obese patients in Korea are receiving Korean medicine (KM) treatment, including herbal medicine and acupuncture, for weight loss. However, the real-world data (RWD) are insufficient in terms of being longitudinal and diverse. Weight Control Registry using KM is a prospective registry study that enrolls patients receiving KM treatment for weight loss and collects RWD from multiple clinics. The patients who are eligible for this study are aged 19-65 years, receive KM weight loss treatment, understand the study objectives, and consent voluntarily. Clinical data of patient characteristics and KM treatment patterns will be regularly collected until 2026. The longitudinal accumulation of various RWD will establish a high-quality study database for KM weight loss treatment. With this study, we expect to contribute to understanding the current trend of weight loss treatment with KM and solve further questions regarding this treatment.

Corporate Social Responsibility: What Are Foodservice Companies Reporting?

This study identified aspects of corporate social responsibility (CSR) activities using online communication tools (i.e., websites and online CSR reports) with an emphasis on the foodservice industry and compared quick-service restaurants and dessert cafes. With the content analysis of 48 foodservice companies, the community, environment, marketplace, vision and values, food, and workforce-centered CSR activities implemented by the selected foodservice companies were measured. In addition, the types CSR information delivered to customers employed by the foodservice companies were investigated. Lastly, there were significant differences between two segments in the foodservice industry in some aspects of CSR activities and types of CSR activities.

Feasibility and Effectiveness of Assessing Subhealth Using a Mobile Health Management App (MibyeongBogam) in Early Middle-Aged Koreans: Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) is a major source of health management systems. Moreover, the demand for mHealth, which is in need of change due to the COVID-19 pandemic, is increasing worldwide. Accordingly, interest in health care in everyday life and the importance of mHealth are growing. OBJECTIVE: We developed the MibyeongBogam (MBBG) app that evaluates the user's subhealth status via a smartphone and provides a health management method based on that user's subhealth status for use in everyday life. Subhealth is defined as a state in which the capacity to recover to a healthy state is diminished, but without the presence of clinical disease. The objective of this study was to compare the awareness and status of subhealth after the use of the MBBG app between intervention and control groups, and to evaluate the app's practicality. METHODS: This study was a prospective, open-label, parallel group, randomized controlled trial. The study was conducted at two hospitals in Korea with 150 healthy people in their 30s and 40s, at a 1:1 allocation ratio. Participants visited the hospital three times as follows: preintervention, intermediate visit 6 weeks after the intervention, and final visit 12 weeks after the intervention. Key endpoints were measured at the first visit before the intervention and at 12 weeks after the intervention. The primary outcome was the awareness of subhealth, and the secondary outcomes were subhealth status, health-promoting behaviors, and motivation to engage in healthy behaviors. RESULTS: The primary outcome, subhealth awareness, tended to slightly increase for both groups after the uncompensated intervention, but there was no significant difference in the score between the two groups (intervention group: mean 23.69, SD 0.25 vs control group: mean 23.1, SD 0.25; P=.09). In the case of secondary outcomes, only some variables of the subhealth status showed significant differences between the two groups after the intervention, and the intervention group showed an improvement in the total scores of subhealth (P=.03), sleep disturbance (P=.02), depression (P=.003), anger (P=.01), and anxiety symptoms (P=.009) compared with the control group. CONCLUSIONS: In this study, the MBBG app showed potential for improving the health, especially with regard to sleep disturbance and depression, of individuals without particular health problems. However, the effects of the app on subhealth awareness and health-promoting behaviors were not clearly evaluated. Therefore, further studies to assess improvements in health after the use of personalized health management programs provided by the MBBG app are needed. The MBBG app may be useful for members of the general public, who are not diagnosed with a disease but are unable to lead an optimal daily life due to discomfort, to seek strategies that can improve their health. TRIAL REGISTRATION: Clinical Research Information Service KCT0003488; https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=14379.

Effects of Acupuncture on Lowering Blood Pressure in Postmenopausal Women with Prehypertension or Stage 1 Hypertension: A Propensity Score-Matched Analysis.

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120-159 mmHg or diastolic blood pressure 80-99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants' diastolic blood pressure (-9.92 mmHg; p < 0.001) and systolic blood pressure (-10.34 mmHg; p < 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.

Robust and distributed neural representation of action values.

Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.

Adult trkB Signaling in Parvalbumin Interneurons is Essential to Prefrontal Network Dynamics.

Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of γ oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.SIGNIFICANCE STATEMENT Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling promotes the maturation of inhibitory parvalbumin (PV) interneurons, neurons central to local cortical dynamics, γ rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphologic alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant local field potential (LFP) activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain.

Network Asynchrony Underlying Increased Broadband Gamma Power.

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband γ power in the local field potential. Increased baseline broadband γ is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband γ is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the γ band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband γ power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike "contamination") affect the broadband γ band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and fragmentation of brain states. Local application of S(+)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband γ power. However, our investigations suggest that disparate mechanisms underlie increased broadband γ power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband γ. Our study confirms that enhanced broadband γ power can arise from asynchronous activities and demonstrates that long-term deficiency of PV inhibition can be a contributor.SIGNIFICANCE STATEMENT Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. γ oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. Synchronous activity of inhibitory parvalbumin (PV) interneurons generates cortical γ oscillation, but, paradoxically, PV neuron deficiency is associated with increases in γ oscillations. We here reconcile this conundrum and show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased γ power. Thus, increased γ power does not always reflect a genuine rhythm. Further, we show that ketamine-induced γ increases are caused by separate network mechanisms.

Effects of Sihogayonggolmoryeo-tang (Saikokaryukotsuboreito or Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) for insomnia disorder with prehypertension or stage 1 hypertension: A study protocol for a randomized controlled trial.

BACKGROUND: Insomnia and hypertension are diseases with a high prevalence and a known association with each other. Sihogayonggolmoryeo-tang (SYM) is an herbal medicine traditionally used for the treatment of insomnia disorder concurrent with hypertension. However, no scientific clinical evidence exists supporting the effects of SYM on these disorders. This study aims to explore the feasibility, effectiveness, and safety of SYM for the treatment of insomnia disorder with concurrent prehypertension or stage 1 hypertension. METHODS: A prospective, randomized, wait-list controlled, parallel, pilot clinical trial has been designed for a study to be conducted in Daejeon, Republic of Korea. Thirty insomnia disorder patients with prehypertension or stage 1 hypertension will be randomly assigned to a SYM or wait-list group at a 1:1 ratio. The SYM group will be administered SYM granules twice a day for 4 weeks and followed-up for 2 weeks while the wait-list group will not receive SYM granules. All participants in both groups will be given brochures with instructions for maintaining sleep hygiene and lifestyle modifications to reduce hypertension. Data will be collected at baseline and at 2, 4, and 6 weeks after allocation. The primary outcome is the Insomnia Severity Index score at 4 weeks post-treatment. The secondary outcomes will consist of the Pittsburgh Sleep Quality Index, sleep diary, systolic and diastolic blood pressure, brachial-ankle pulse wave velocity, ankle-brachial index, atherosclerosis biomarkers, the Hospital Anxiety and Depression Scale, the 5-level EuroQol-5 dimensions, and the Patient Global Impression of Change. Adverse events and laboratory test results will be monitored to assess the safety. Data will be recorded in electronic case report forms and analyzed using SPSS Statistics, Version 24.0. DISCUSSION: This is the first clinical trial to explore the effectiveness and safety of SYM for the treatment of insomnia disorder concurrent with prehypertension or stage 1 hypertension. The results of this study can form the foundation for a future multicenter, large-scale, confirmatory clinical trial. TRIAL REGISTRATION: Clinical Research Information Service, KCT0005001 (registered on May 8, 2020).

The DMCdrive: practical 3D-printable micro-drive system for reliable chronic multi-tetrode recording and optogenetic application in freely behaving rodents.

Electrophysiological recording and optogenetic control of neuronal activity in behaving animals have been integral to the elucidation of how neurons and circuits modulate network activity in the encoding and causation of behavior. However, most current electrophysiological methods require substantial economical investments and prior expertise. Further, the inclusion of optogenetics with electrophysiological recordings in freely moving animals adds complexity to the experimental design. Expansion of the technological repertoire across laboratories, research institutes, and countries, demands open access to high-quality devices that can be built with little prior expertise from easily accessible parts of low cost. We here present an affordable, truly easy-to-assemble micro-drive for electrophysiology in combination with optogenetics in freely moving rodents. The DMCdrive is particularly suited for reliable recordings of neurons and network activities over the course of weeks, and simplify optical tagging and manipulation of neurons in the recorded brain region. The highly functional and practical drive design has been optimized for accurate tetrode movement in brain tissue, and remarkably reduced build time. We provide a complete overview of the drive design, its assembly and use, and proof-of-principle demonstration of recordings paired with cell-type-specific optogenetic manipulations in the prefrontal cortex (PFC) of freely moving transgenic mice and rats.

Association between fatigue, pain, digestive problems, and sleep disturbances and individuals' health-related quality of life: a nationwide survey in South Korea.

BACKGROUND: Physical symptoms such as fatigue, pain, digestive problems, and sleep disturbances are chief reasons individuals seek primary care, as they affect health-related quality of life. We investigated the associations between various combinations of these common symptoms and individuals' health-related quality of life. METHODS: This large-scale survey study of 1100 Koreans aged ≥19 years was conducted in 2017 using multi-stage stratified sampling based on region, sex, and age. Data were collected using questionnaires administered face-to-face; then, a linear regression analysis was performed to assess how the symptoms were related to participants' health-related quality of life. Complex symptoms were defined as co-occurrence of two or more of the four symptoms-fatigue, pain, digestive problems, and sleep disturbances. RESULTS: The most frequently observed stand-alone symptom was fatigue, while the most common combination was fatigue and pain. When examined individually, fatigue, digestive problems, and sleep disturbances were closely associated with mental health-related quality of life, and pain was associated with physical health-related quality of life. Complex symptoms were also related to health-related quality of life. Lower physical health-related quality of life was strongly associated when fatigue and pain or all four symptoms were co-occurring, and the lowest mental health-related quality of life was seen when all four symptoms were present, after adjusting for all variables. CONCLUSIONS: Symptoms can be present in various combinations and are significantly associated with health-related quality of life. Extra attention should be given to patterns accompanying fatigue and pain and to those involving more symptoms. This elucidated the characteristics of symptoms that affect the health-related quality of life of South Korean adults.

Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis.

BACKGROUND: Osteoporosis is related to the number and activity of osteoclasts. The goal of the present study was to demonstrate the effect of Chaenomelis Fructus (CF) on osteoclastogenesis and its mechanism of bone loss prevention in an OVX-induced osteoporosis model. METHODS: Osteoclasts were induced by RANKL in RAW 264.7 cells. TRAP assay was performed to measure the inhibitory effect of CF on osteoclast differentiation. Then, Expression of nuclear factor of activated T-cells (NFATc1), c-Fos which are essential transcription factors in osteoclastogenesis were detected using western blot and RT-PCR. The osteoclast-related markers were measured by RT-PCR. Moreover, the ability of CF to inhibit bone loss was researched by ovariectomized (OVX)-induced osteoporosis. RESULTS: Cell experiments showed that CF inhibited osteoclast differentiation and its function. Immunoblot analyses demonstrated that CF suppressed osteoclastogenesis through the NFATc1 and c-Fos signaling pathways. RT-PCR determined that CF inhibited osteoclast-related markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTK), osteoclast-associated immunoglobulin-like receptor (OSCAR), ATPase H+ Transporting V0 Subunit D2 (ATP6v0d2) and carbonic anhydrase II (CA2). In animal experiments, CF showed an inhibitory effect on bone density reduction through OVX. Hematoxylin and eosin (H&E) staining analysis data showed that CF inhibited OVX-induced trabecular area loss. TRAP staining and immunohistochemical staining analysis data showed that CF displayed an inhibitory effect on osteoclast differentiation through NFATc1 inhibition in femoral tissue. CONCLUSION: Based on the results of in vivo and in vitro experiments, CF inhibited the RANKL-induced osteoclasts differentiation and its function and effectively ameliorated OVX-induced osteoporosis rats.

Publisher Correction: A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse.

The Supplementary Information is available in the online version of this Publisher Correction.

A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse.

The local and long-range connectivity of cortical neurons are considered instrumental to the functional repertoire of the cortical region in which they reside. In cortical networks, distinct cell types build local circuit structures enabling computational operations. Computations in the medial prefrontal cortex (mPFC) are thought to be central to cognitive operation, including decision-making and memory. We used a retrograde trans-synaptic rabies virus system to generate brain-wide maps of the input to excitatory neurons as well as three inhibitory interneuron subtypes in the mPFC. On the global scale the input patterns were found to be mainly cell type independent, with quantitative differences in key brain regions, including the basal forebrain. Mapping of the local mPFC network revealed high connectivity between the different subtypes of interneurons. The connectivity mapping gives insight into the information that the mPFC processes and the structural architecture underlying the mPFC's unique functions.

Three-Component Herbal Tea Alleviates Prolonged Fatigue and Improves Sleep Quality: A Randomized Controlled Pilot Study.

INTRODUCTION: Prolonged fatigue is common among adults, yet only a small percentage of affected individuals seek medical attention. Following findings that complementary and alternative medicine can be effective strategies for improving fatigue, we evaluated the effect of an herbal tea regimen on prolonged fatigue. METHODS: In this pilot randomized controlled trial, participants with prolonged fatigue were randomly allocated to either a tea (n = 20) or control (n = 20) group. The tea group consumed herbal tea consisting of Astragali Radix, Angelicae gigantis Radix, and Zizyphi Fructus twice daily for 4 weeks, whereas the control group received no intervention. Outcomes were assessed at baseline and 4 and 8 weeks. The primary outcome was fatigue severity, measured using the Chalder Fatigue Scale. Secondary outcomes included sleep quality, depression symptoms, and quality of life. RESULTS: Among the 40 individuals screened, 35 completed the study. Fatigue severity was significantly lower in the tea group than the control group at 4 weeks, and within the tea group, fatigue severity and sleep quality improved at the 4- and 8-week follow-ups vs. baseline in the tea group. Depression also significantly improved in the tea group at 8 weeks. There were no changes within the control group on any measure. CONCLUSION: The findings suggest that our herbal tea formulation reduces fatigue severity and improves sleep quality in adults with prolonged fatigue.

Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury.

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.

Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network.

How autoreceptors contribute to maintaining a stable output of rhythmically active neuronal circuits is poorly understood. Here, we examine this issue in a dopamine population, spontaneously oscillating hypothalamic rat (TIDA) neurons, that underlie neuroendocrine control of reproduction and neuroleptic side effects. Activation of dopamine receptors of the type 2 family (D2Rs) at the cell-body level slowed TIDA oscillations through two mechanisms. First, they prolonged the depolarizing phase through a combination of presynaptic increases in inhibition and postsynaptic hyperpolarization. Second, they extended the discharge phase through presynaptic attenuation of calcium currents and decreased synaptic inhibition. Dopamine reuptake blockade similarly reconfigured the oscillation, indicating that ambient somatodendritic transmitter concentration determines electrical behavior. In the absence of D2R feedback, however, discharge was abolished by depolarization block. These results indicate the existence of an ultra-short feedback loop whereby neuroendocrine dopamine neurons tune network behavior to echoes of their own activity, reflected in ambient somatodendritic dopamine, and also suggest a mechanism for antipsychotic side effects.