bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPACT OF COVID-19 INFECTION AND RELATED SOCIAL CONCERNS ON DEPRESSIVE SYMPTOMS: MEDIATING EFFECTS OF DAILY LIFE RESTRICTION
Authors: Ho *Dham , Park Min-A , Lim Weon-Jeong 
Published: February 2025

Abstract

Background
As the COVID-19 outbreak persisted, the accompanying increase in depression had emerged as a significant issues.

Aims & Objectives
This study examined the mediating effect of daily life restriction after COVID-19 pandemic on depressive symptoms, considering COVID-19 infection or social concerns about COVID-19 infection. Additionally, comparisons of path coefficients between groups were conducted based on gender and age.

Method
Data derived from the 2020 Korean Community Health Survey (KCHS) consisted of 229,269 individuals aged 19 to 110. This study used self-reported questionnaire including Patient Health Questionnaire-9 (PHQ-9), three items addressing social concerns related to COVID-19 infection (concerns about blame from the surroundings, economic impact, and infection of vulnerable family members), a self-questionnaire to confirm whether individuals had experienced quarantine or hospitalization due to COVID-19 infection within last 3 months, and scores of daily life restriction due to the COVID-19 pandemic. Structural equation model analysis was conducted to identify whether daily life restriction serves as a mediating factor in the association between COVID-19 infection and related social concerns and depressive symptoms. In addition, chi-square tests for comparing path coefficients based on age (below 65 years old, 65 and older) and gender were conducted.

Results
Structural equation models revealed significant direct effects of COVID-19 infection and related social concerns on depressive symptoms (COVID-19 infection to PHQ-9: β = 0.011, p &lt;0.01; social concerns about COVID-19 infection to PHQ-9: β = 0.049, p &lt;0.01), along with indirect effects through daily life restrictions after the COVID-19 pandemic on PHQ-9 symptoms (COVID-19 infection to PHQ-9: β = 0.014, p &lt;0.01; social concerns about COVID-19 infection to PHQ-9: β = 0.001, p &lt;0.01). When comparing path coefficients between subgroups based on age and gender, path coefficients associated with depression were higher in the groups under 65 years of age and females.

Discussion & Conclusions
Considering the impact of daily life restrictions on depression related to COVID-19 infection and related social concerns is essential, and more attention is needed for women and individuals under age of 65.
CALBINDIN-POSITIVE PYRAMIDAL NEURONS IN HIPPOCAMPAL CA1 MEDIATE EARLY-LIFE STRESS-INDUCED COGNITIVE IMPAIRMENT IN MICE
Authors: Li *Xuexin , Sun Yaxin , Su Yunai , Li Jitao , Si Tianmei 
Published: February 2025

Abstract

Background
Early-life stress (ELS) can cause persistent and irreversible damage to the development, plasticity, and cognitive function of the hippocampus, leading to depression and other mental illnesses. However, the mechanism of negative effects induced by ELS remained unclear.

Aims & Objectives
Calbindin (CB) is one of the molecular markers of the superficial pyramidal neurons (PNs) of the hippocampal CA1 area. Previous research found that calbindin-positive (CB+) PNs and calbindin-negative (CB-) PNs in hippocampal dorsal CA1 (dCA1) region may play distinct roles in the regulation of cognition. Thus, the aim of this study was to explore the mechanism of different types of PNs in mediating ELS- induced cognitive deficits, and to provide new insights for the prevention and treatment of the stress- related mental disorders such as depression.

Method
We adopted the early-life stress model of the "limited bedding and nesting materials", and explored its impact on cognitive functions as well as neural activity and morphological plasticity of CB+ PNs and CB- PNs in dCA1 using behavioral, morphological and molecular biology techniques. Then, we selectively inhibited or activated CB+ PNs or CB- PNs in dCA1 with combination of transgenic mice and chemogenetic techniques to investigate the roles of different types of PNs in mediating cognitive impairment induced by ELS.

Results
ELS significantly impaired the cognitive performance in spatial object recognition (SOR) task, as well as the c-Fos expression of PNs in dCA1 after SOR task, with the activation of CB+ PNs outweighing CB- PNs. The dendritic complexity of CB+ PNs was damaged by ELS, but remained unaffected for CB- PNs. Specific inhibition of CB+ PNs in dCA1 mimicked the negative effect of ELS on cognitive functions, while inhibition of CB- PNs did not. Specific activation of CB+ PNs in dCA1 successfully reversed the cognitive impairment caused by ELS, whereas activation of CB- PNs failed to do so.

Discussion & Conclusion
Our findings indicate that calbindin-positive pyramidal neurons in dorsal hippocampal CA1 mediate the mechanism of cognitive impairment induced by early-life stress. Thus, calbindin-positive neurons in hippocampal CA1 may present new target for the prevention and treatment for cognitive dysfunction in stress-related mental illnesses such as depression.
ADOLESCENT BINGE DRINKING INDUCES BEHAVIORAL ABNORMALITIES IN ADULTHOOD CAUSED BY MYELIN ABNORMALITIES
Authors: Kunisawa *Kazuo , Sugawara Yumika , Yoshidomi Kohei , Kon Yuki , Saito Kuniaki , Nabeshima Toshitaka , Mouri Akihiro 
Published: February 2025

Abstract

Background
Adolescent binge drinking represents a major public health challenge and lead to persistent psychiatric disorders. However, the underlying pathogenic mechanisms remain poorly understood. Myelin abnormalities were observed in human subjects with alcohol abuse.

Aims & Objectives
In the present study, we investigated whether myelin abnormalities are involved in behavioral abnormalities induced by adolescent binge ethanol treatment (ABET).

Method
To produce ABET, C57BL/6J mouse was given EtOH (3.0g/kg, i.g. 25% ethanol w/v) once a day during adolescence (P28-46) in an intermittent fashion.

Results
ABET persistently developed behavioral abnormalities such as anxiety-like behaviors in the marble burying test and the novelty suppressed feeding test, impaired memory function in the novel object recognition test, and impairment of social interaction. ABET decreased myelin-related protein and mature oligodendrocytes through impaired oligodendrogenesis in the prefrontal cortex and hippocampus. Inhibiting adolescent myelination by deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursor cells increased susceptibility to behavioral abnormalities induced by a subthreshold ABET, while promoting oligodendrogenesis and myelination via clemastine treatment rescues the ABET-induced behavioral abnormalities.

Discussion & Conclusion
These findings suggest that myelin abnormalities caused by ABET may be involved in the behavioral abnormalities in adulthood.
THE INFLUENCE OF DISSOCIATIVE RESPONSE ON CORTISOL LEVEL FOLLOWING CHILDHOOD AND LATER TRAUMA: A PATH ANALYSISTHE INFLUENCE OF DISSOCIATIVE RESPONSE ON CORTISOL LEVEL FOLLOWING CHILDHOOD AND LATER TRAUMA: A PATH ANALYSIS
Authors: Yang *Chaeyeon , Kwon Aeran , Jung Bori , Lee Seung-Hwan 
Published: February 2025

Abstract

Background
Exposure to trauma during childhood can increase a risk of later traumatic experiences and dissociative responses. Furthermore, several studies found that dissociation is related with cortisol levels.

Aims & Objectives
In this study, we examined the impact of dissociative responses to traumatic experiences on cortisol levels in the general population with traumatic experiences.

Method
A total of one hundred seventy-five participants were recruited and had their morning cortisol levels measured. Clinical assessments were performed, including the Childhood Trauma Questionnaire (CTQ), Life Events Checklist (LEC), Peritraumatic Dissociative Experiences Questionnaire (PDEQ). Partial correlation and path analyses were conducted controlling age, sex, years of education, and BMI.

Results
Partial correlation showed that childhood trauma was positively correlated with later traumatic events and dissociation. In addition, multiple path analysis indicated that the direct effects of childhood trauma on later trauma, childhood trauma on dissociation, later trauma on dissociation, and dissociation on cortisol level were significant. However, partial mediation model which added a direct path from childhood trauma to cortisol level was insignificant.

Discussion & Conclusion
These findings suggest that dissociation is a critical factor related to altered cortisol levels in people who experienced childhood and later traumatic events.
(2R,6R)-HYDROXYNORKETAMINE TARGETING THE BASOLATERAL AMYGDALA REGULATES FEAR MEMORY
Authors: Xu *Yuanyuan , Li Zhenlong , Lee Chau-Shoun , Peng Hsien-Yu , Lin Tzer-Bin , Hsieh Ming-Chun , Lai Cheng-Yuan , Chou Dylan 
Published: February 2025

Abstract

Background
(2R,6R)-Hydroxynorketamine (HNK), a ketamine metabolite, is a promising next-generation antidepressant known for its rapid and long-lasting effects. Recent studies have explored its impact on memory, yet its influence on fear memory extinction remains uncharted.

Objective
We investigated (2R,6R)-HNK's effects on synaptic transmission and plasticity in the basolateral amygdala (BLA) and its role in auditory fear memory extinction.

Method
Adult male C57BL/6J mice were utilized for extracellular electrophysiological recordings and fear conditioning tests.

Result
(2R,6R)-HNK at 30 mg/kg increased cfos-positive cell count in the BLA and dose-dependently enhanced long-term potentiation (LTP) induction and maintenance. Moreover, (2R,6R)-HNK improved BLA synaptic transmission. Both local and systemic administration of (2R,6R)-HNK reduced recent and remote fear memory retrieval and inhibited spontaneous remote fear memory recovery.

Conclusion
(2R,6R)-HNK could be a potential treatment for posttraumatic stress disorder (PTSD) patients by regulating BLA synaptic function and fear memory modulation.
BEHAVIORAL ANALYSIS OF MOTIVATED-BEHAVIOR-DEFICITS IN PACLITAXEL-INDUCED NEUROPATHY MODEL MICE
Authors: Otsuki *Tomofumi , Junqueira Joao Pedro , Matsumoto Jumpei , Setogawa Tsuyoshi , Uta Daisuke , Nishimaru Hiroshi 
Published: February 2025

Abstract
Numerous clinical studies have shown that chronic pain patients very often suffer from affective disorders, such as depression accompanied by decreased motivation. It has been proposed that they share a common neuronal mechanism since it has been reported that the rate of psychiatric disorders in chronic pain patients is approximately two to three times higher than in non-patients (McWilliams et al. Pain, 106:127-133, 2003). Central sensitization is one of the prominent hypotheses for the neuropathology of chronic pain of which pain information is abnormally amplified in the brain due to altered function of sensory-related regions which also affects emotion-related regions as well. Several preclinical studies have shown that deficit in motivated-behavior in animal persistent-pain models. However, the underlying neuronal mechanism remains largely unraveled. In rodents, locomotion is known to be essential for seeking and obtaining reward while licking behavior have been indicated as a crucial behavioral signal for expectation of reward. In this study, we examined these behavioral parameters in a paclitaxel-induced peripheral neuropathy (PIPN) mouse model. These mice exhibit mechanical allodynia and depression-like behavior for 2-3 weeks after intraperitoneal injection of paclitaxel (Toma et al. Neuropharmacology 17:305–315, 2017). We examined their changes of behavioral parameters during operant conditioning task that enabled us to quantitatively analyze licking and locomotion. Mice were water-restricted, placed on a polystyrene disc with their head fixed and trained to perform a locomotor operant task that required them to start running spontaneously to trigger the following trial. After running for 1 second, a drop of water was delivered from the spout as a reward, followed by a 2 second quiescence period. Trained mice achieved success rate over 80 % after 8-10 sessions were randomly assigned to PIPN group (n = 6) or control group (n = 7) and examined task performance for 4 weeks. PIPN mice showed altered performance during the second week after injection. During this period, the mean success rate in PIPN group significantly dropped (as low as 66%) but not in control group. In unsuccessful trials, mice typically stopped prematurely before reaching the goal. Moreover, the frequency of anticipatory licking significantly decreased in PIPN mouse. However, total running distance during the task remained unchanged. These results indicate that PIPN mice show deficits in motivational behavioral parameters during the period which they go through persistent pain. The behavioral paradigm in this study could be a useful to study mouse pain models to elucidate the neuronal mechanism of deficits in motivational behavior. This work was supported by JST SPRING, Grant Number, JPMJSP2145 (TO), Tamura Science &Technology Foundation (HN), Takeda Science Foundation (HN), KAKENHI No, 23H04673 (HN).
INHIBITION OF HISTAMINE METABOLIZING ENZYME IN THE BRAIN REDUCES CATAPLEXY IN NARCOLEPSY MODEL MICE
Authors: Yoshikawa *Takeo , Girgin Birkan , Agu Anne Bernadette , Nakamura Tadaho , Yanai Kazuhiko , Mochizuki Takatoshi , Nagasawa Shota , Iwabuchi Yoshiharu , Naganuma Fumito 
Published: February 2025

Abstract
Histamine plays a role as neurotransmitter to exert wake-promoting effects in the brain. Decreased histamine concentration in cerebrospinal fluid of narcolepsy patients suggested that the dysfunction of histamine system in the patients was involved in narcolepsy pathophysiology, suggesting that drugs increasing brain histamine level ameliorated narcolepsy symptoms. Thus, we hypothesized that inhibition of histamine metabolizing enzyme, histamine N-methyltransferase (HNMT), could increase brain histamine concentration and alleviate cataplexy by activating histamine system. First, we examined the pharmacological actions of metoprine, a HNMT inhibitor, on wild type mice. Metoprine significantly increased histamine contents in the brain but not lung, skin and stomach, however, metoprine did not change the concentrations of other monoamines such as dopamine, serotonin and norepinephrine. EEG (electroencephalogram) recording and pharmacological assays revealed that elevated histamine extended wakefulness of wild type mice by the activation of histamine H1 receptors. Next, we investigated the therapeutic potential of metoprine on narcolepsy model mice. Administration of metoprine significantly reduced the number and duration of cataplexy in the model mice. Although we confirmed the therapeutic effect of pitolisant, which increases brain histamine release and is approved in USA and EU for the narcolepsy treatment, the efficacy of metoprine was better than that of pitolisant, emphasizing the sufficient therapeutic potential of HNMT inhibitors against narcolepsy. Unfortunately, there was no HNMT inhibitors with high permeability of blood-brain barrier and high specificity. Thus, we performed compound screening to obtain novel HNMT inhibitors available for narcolepsy treatment. After the structural optimization of candidate compounds, we got several compounds with low IC50 values to HNMT enzymatic activity.In the present study, we demonstrated that elevated brain histamine by HNMT inhibition robustly induced wakefulness and improved the symptoms of narcolepsy model mice. Further studies are essential to obtain therapeutic compounds for the treatment of human narcolepsy.
POGZ MUTANT MOUSE MODEL OF AUTISM SPECTRUM DISORDER SHOWS ABNORMAL NEURAL ACTIVITY IN THE ANTERIOR CINGULATE CORTEX DURING SOCIAL BEHAVIOR
Authors: Kitagawa *Kohei , Takemoto Tomoya , Seiriki Kaoru , Kasai Atsushi , Hashimoto Hitoshi , Nakazawa Takanobu 
Published: February 2025

Abstract

Background
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication. Despite its high prevalence, neural pathogenesis of ASD is largely unknown. The anterior cingulate cortex (ACC) is critically involved in various cognitive processes and has been reported to be associated with social communication. Recent studies suggest that impaired ACC function may be associated with social impairment in ASD, however the detailed underlying neural mechanisms are unclear. We previously demonstrated that a mouse model carrying an ASD patient-derived mutation in POGZ, one of the genes most significantly associated with ASD (POGZ mutant mice), showed ASD-like behavioral deficits, including impaired social communication.

Aims & Objectives
Here, to understand the neural mechanisms behind the impaired social communication in POGZ mutant mice, we measured the neural activity in the ACC by fiber photometry in freely moving mice.

Methods
Fiber photometry was employed to examine neural activities in freely moving mice participating in social interaction tests. Wild-type (WT) and POGZ mutant mice were injected with AAV-CamKIIα-GCaMP6f in the ACC, followed by the implantation of optic cannula. Ca2+ signals were recorded during 5-minute social interaction tests, at a minimum of 3 weeks post-injection.

Results
We initially confirmed that POGZ mutant mice exhibited reduced social interaction time compared to their WT littermates, consistent with our previous report. Through fiber photometry recordings, we observed an elevation in Ca2+ signals of ACC pyramidal neurons upon the introduction of intruder mice in both WT and POGZ mutant mice. Remarkably, the average Ca2+ signals of ACC pyramidal neurons in the presence of intruder mice were significantly higher in POGZ mutant mice. In contrast, the neural activity in the ACC pyramidal neurons in POGZ mutant mice displayed reduced responsiveness to the initiation of each social investigation in comparison to that in WT mice. These results suggest that the ACC neural activity governing social behavior is impaired in POGZ mutant mice.

Discussion & Conclusion
These findings suggest a neurobiological link between the dysregulation of neural activity in ACC pyramidal neurons and social impairment in POGZ mutant mice, thereby shedding light on potential avenues for the development of novel therapeutics for ASD.
MICROBIAL METABOLITES REGULATE SOCIAL NOVELTY VIA CAMKII NEURONS IN THE BNST
Authors: Liou Chia-Wei , Cheng Sin-Jhong , Yao Tzu-Hsuan , Lai Tzu-Ting , Tsai Yu-Hsuan , Wu *Wei-Li 
Published: February 2025

Abstract

Background
Social novelty is a cognitive process that is essential for animals to interact strategically with conspecifics based on their prior experiences. The commensal microbiome in the gut modulates social behavior through various routes, including microbe-derived metabolite signaling.

Aims & Objectives
Short-chain fatty acids (SCFAs), metabolites derived from bacterial fermentation in the gastrointestinal tract, have been previously shown to impact host behavior.

Method
We interrogate the functional role of SCFAs in the brain and social behavior via intracerebroventricular infusion of SCFAs in freely moving mice. Electrophysiology, chemogenetic manipulation, and Cre- dependent cell ablation were employed to unravel the neural circuit by which SCFAs alter social behavior.

Results
Herein, we demonstrate that the delivery of SCFAs directly into the brain disrupts social novelty through distinct neuronal populations. We observed that infusion of SCFAs into the lateral ventricle disrupted social novelty in microbiome-depleted mice without affecting brain inflammatory responses. The deficit in social novelty can be recapitulated by activating calcium/calmodulin-dependent protein kinase II (CaMKII)-labeled neurons in the bed nucleus of the stria terminalis (BNST). Conversely, chemogenetic silencing of the CaMKII-labeled neurons and pharmacological inhibition of fatty acid oxidation in the BNST reversed the SCFAs-induced deficit in social novelty.

Discussion & Conclusion
Our findings suggest that microbial metabolites impact social novelty through a distinct neuron population in the BNST.

References
Liou CW, Cheng SJ, Yao TH, Lai TT, Tsai YH, Chien CW, Kuo YL, Chou SH, Hsu CC, Wu WL. Microbial metabolites regulate social novelty via CaMKII neurons in the BNST. Brain Behav Immun. 2023 Oct;113:104-123. doi: 10.1016/j.bbi.2023.06.029. Epub 2023 Jun 29. PMID: 37393058.
IMPORTANCE OF β-PHENYLETHYLAMINE (PEA) NEURONAL SYSTEM, EQUIVALENT TO D-NEURON SYSTEM AND TAAR1 LIGAND NEURON SYSTEM
Authors: Ikemoto *Keiko 
Published: February 2025

Abstract

Background
β-phenylethylamine (PEA) is a trace amine, recently regarded as a neurotransmitter, rather than a neuromodulator, of which chemical structure is similar to amphetamine, mescaline or catecholamines. The PEA neuron may have aromatic L-amino acid decarboxylase (AADC) as a synthesizing enzyme, TAAR1 as a receptor, and MAOB as a degrading enzyme [1, 2, 3].

Aims & Objectives
PEA affects on animal behaviours and human mental states. TAAR1 medicinal chemistry is prospective psychopharmacological field. The present study highlights PEA neuronal system.

Methods
Brains of mice, rats, monkeys and MAOA KO mice, and human post-mortem brains were used. AADC immunohistochemistry and MAO enzyme histochemistry was applied.

Results
Distribution of mouse D-neurons was overall overlapped with MAOB-positive neurons shown by applying MAO enzyme histochemistry to MAOA KO mice. In humans, D-neuron system was developped in the thalamus, striatum and nucleus accumbens, compared to rodents and monkeys. D-neuron system had distinct species differences.

Discussion & Conclusion
There are accumulating evidences showing that PEA neuronal system is equivalent to D-neuron system and TAAR1 ligand neuron system. Understanding of this neuronal system would serve to develop treatment of neuropsychiatric disaeses and TAAR1 medicinal chemistry.

References
1Grimsby J et al. Nat Genet 17: 206-210, 1997
2Ikemoto K et al. Brain Res 771: 121-132, 1997
3Ikemoto K et al. In: Trace Amine and Neurological Disorders, Eds Tahira Farooqui &Akhlaq A Farooqui, pp.295-307, 2016
NEURONAL CIRCUITS AND NEURONAL MEMBRANE PROPERTIES INVOLVED IN EMPATHY
Authors: Yoshida *Takayuki , Youdai Umakoshi , Hashimoto Kouichi 
Published: February 2025

Abstract
Empathy is a cognitive and emotional response that occurs in individuals who observe the experiences of others. In this study, we aimed to understand the neural circuit mechanisms involved in empathy by using the observational fear learning (OFL) test, immunohistochemical (IHC) and patch-clamp (PC) analyses in mice. We labeled pyramidal cells in the dorsal medial prefrontal cortex (dmPFC) that project to the basolateral lateral amygdala (BLA) or periaqueductal gray (PAG) and control fear and its associated behaviors, respectively, and analyzed the neuronal activity induced by OFL using c-fos expression as an indicator for IHC analysis. PAG projection neurons were both activated by about 15%. PC analysis of the membrane potential properties of dmPFC pyramidal cells under normal conditions revealed that BLA- or PAG-projecting pyramidal cells fired action potentials more frequently than did non-projecting pyramidal cells. These results suggest that BLA- or PAG-projected dmPFC pyramidal cells express empathy by suppressing their excitability.