bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEUROFILAMENT LIGHT CHAIN AS A POTENTIAL INDICATOR OF DELIRIUM TREMENS AMONG PATIENTS WITH ALCOHOL DEPENDENCE
Authors: Hou *Yu Chi , Huang Ming Chyi , Liu Tung Hsia , Liu Yu Li 
Published: February 2025

Abstract

Background
Delirium tremens (DTs) is the most serious complication of alcohol withdrawal syndrome in patients with alcohol dependence (AD) as it is associated with high risk of mortality rate if not recognized promptly and treated adequately. Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in AD(Huang et al., 2023). However, whether NFL level differs between patients with and without DTs has not been explored yet.

Aims & Objectives
We compared the blood NFL levels between patients with AD who had experience of DTs and those did not to test the hypothesis that NFL can identify the patients with AD to develop DTs.

Methods
224 inpatients fulfilled the DSM-IV-TR criteria for AD and 116 healthy controls were enrolled. Patients with AD were divided by the appearance of DTs into the DT group (n = 25) and non-DT group (n = 199). Blood levels of NFL were measured by Ella microfluid platform analysis. We performed the receiver operating characteristic (ROC) analysis to determine the possibility of NFL level to discriminate individuals with DTs.

Results
Serum NFL levels differed significantly among the three groups, with highest in the DT group (63.1 ± 47.2 pg/mL), followed by non-DT group (24.0 ± 22.4 pg/mL) and then control group (11.8 ± 6.1 pg/mL) (p &lt;0.0001). In addition, the ROC curve revealed that an NFL level of 31.2 pg/mL could significantly differentiate DTs group from non-DT group (sensitivity: 80.0%; specificity: 76.9%; area under the curve: 0.84; p &lt;0.001; 95% Confidence Intervals for the AUC: 0.77-0.91).

Discussion & Conclusion
Our study revealed the patients with AD experiencing DTs had a significantly higher NFL level, compared to those without such experiences. This result indicate the NFL can be an indicator of delirium tremens in patients with alcohol dependence.Furthermore, the pronounced increase of NFL levels in the patients with AD warrants further investigation of a potential neuroaxonal vulnerability of patients with AD to the development of DTs.

References
HUANG, M. C., TU, H. Y., CHUNG, R. H., KUO, H. W., LIU, T. H., CHEN, C. H., MOCHLY-ROSEN, D. &LIU, Y. L. 2023. Changes of neurofilament light chain in patients with alcohol dependence following withdrawal and the genetic effect from ALDH2 Polymorphism. Eur Arch Psychiatry Clin Neurosci.
NEUROPSYCHOLOGICAL FEATURES AS MEDIATORS BETWEEN PSYCHOPATHOLOGIES AND HEART RATE VARIABILITY: THE SEX DEFFERENCES
Authors: Huang *Wei-Lieh , Liao Shih-Cheng , Wu Chi-Shin , Chiu Yi-Ting 
Published: February 2025

Abstract

Background
Heart rate variability (HRV), as an index of parasympathetic activity, has been reported to be lower in individuals with common mental disorders (depression, anxiety, and somatic symptoms) than in healthy individuals in previous studies. Several meta-analyses have supported this result, but the effect sizes of the differences between patients and healthy individuals are mostly low to moderate, making it difficult for small sample studies to demonstrate between-group differences. Therefore, the mechanisms underlying the link between the psychopathologies of common mental disorders and HRV require further investigation. In recent years, the theory of the frontal-vagal network has gained increasing attention. Furthermore, the relationship between psychopathologies and HRV has been reported to differ between sexes.

Aims & Objectives
Under the hypothesis that disorder status affects cognitive function, we examined whether neuropsychological features can be mediators between psychopathologies and HRV and possible sex differences.

Method
We recruited 359 individuals with and without common mental disorders. Questionnaires were used to measure their psychopathologies. Eight tests from the Cambridge Neuropsychological Test Automated Battery were selected to measure neuropsychological functions. Resting-state HRV measurements were obtained for 5 min. The associations among these constructs were analyzed using multiple linear regression analysis and structural equation modelling.

Results
When psychopathologies and neuropsychological features were simultaneously included as independent variables, most psychopathologies did not exhibit significant associations with HRV. Among women, Reaction Time (RTI, a task of psychomotor speed) indicator mediated the relationship between depression and low-frequency power (LF); Emotion Recognition Task (ERT, a task of emotional regulation) indicator mediated the relationship between health anxiety and high-frequency power (HF). Among men, Intra-Extra Dimensional Set Shift (IED, a task of shifting) indicator mediated the relationship between depression and LF; Match to Sample Visual Search (MTS, a task of selective attention) indicator mediated the relationship between health cognition and HF. The depression-RTI-LF pathway in women tended to lower HRV; whereas health anxiety-ERT-HF in women, depression-IED-LF and health cognition-MTS-HF in men tended to increase HRV.

Discussion & Conclusion
Our findings support the notion that neuropsychological features mediate the relationship between psychopathologies and HRV, and that sex differences exist.
THE FATTY ACID AMIDE HYDROLASE ENZYME INHIBITION IN GLOBUS PALLIDUS CAUSES PANICOLYTIC LIKE EFFECT IN PREY THREATNED BY BOTHROPS JARARACA
Authors: Da Silva Juliana Almeida , Falconi-Sobrinho Luiz Luciano , De Paiva Yara Bezerra , Almada Rafael Carvalho , Coimbra *Norberto Cysne 
Published: February 2025

Abstract
The endocannabinoid modulation of fear and anxiety due to their on-demand synthesis and degradation is supported by a large body of research. Although it has been proposed that the anandamide (AEA) in the globus pallidus (GP) seems to be important for the modulation of innate fear-related behaviours, a role for endogenous AEA has yet to be clarified. Rats were treated with the fatty acid amide hydrolase (FAAH) selective inhibitor URB597 at different concentrations (0.01, 0.1, 1 nmol/ 0.1 &micro;L) in the GP followed by bicuculline microinjections in dlSC and confronted by a lancehead pit viper (Bothrops jararaca) in the enriched polygonal arena for snake panic test. The most effective dose of URB597 (1 nmol) was also preceded by microinjections of the CB1 receptor antagonist AM251 (0.1 nmol) in the GP, and rats were then confronted by venomous snakes. URB597 (0.1 and 1 nmol) in the GP decreased the expression of defensive behaviours such as defensive attention, escape, and time spent inside the burrow of animals confronted by pit vipers. Moreover, the pretreatment of the GP with AM251 suppressed these antiaversive effects of URB597 in such midbrain structure. Overall, these data clearly indicate that the panicolytic consequences of the endogenous AEA enhancement in the GP are mediated by CB1 receptors signalling.
IGFBP2 ATTENUATES RESTRAIN STRESS-INDUCED ANXIETY-LIKE BEHAVIOR VIA MODULATING THE MYELINATION AND SYNAPTIC PLASTICITY IN THE MEDIAL PREFRONTAL CORTEX
Authors: Zhang *Ying-Dan , Shi Dong-Dong , Zhang Sen , Wang Zhen 
Published: February 2025

Abstract

Background
Exposure to stress markedly impairs the emotional functions of the highly evolved prefrontal association cortex (PFC). However, the underlying molecular mechanisms are poorly understood and limited options for treatment. Our previous study has found that the level of IGFBP2 in serum is related to stress resilience in individuals. Insulin-like growth factor binding protein 2 (IGFBP2), a neurotrophic factor, has been associated with neurite outgrowth and synaptic plasticity in central nervous system, enhancing stress resilience.

Aim
To examine the protective effects of IGFBP-2 on stress related disorder and explore its mechanism in SD rats and provide new targets for the intervention.

Method
Here, using a model of restrain stress (RS), we found that RS induces obvious anxiety-like behavior in the open field (OFT) and elevated plus maze test (EPM). RNA-sequencing was further applied to analyze the molecular mechanisms of mPFC following RS. Then we injected IGFBP2 by tail vein administrations to evaluate the anxiolytic effect of IGFBP2. Immunofluorescence and electron microscopy experiments were applied to verify the effect of IGFBP2 on RS-induced brain structural and functional abnormalities.

Result
RS enhances susceptibility to anxiety-like behavior in rats, with injured myelination in mPFC. Systemic delivery of IGFBP2 significantly attenuated anxiety-like behavior in OFT and EPM. Besides, IGFBP2 treatment rats showed enhanced myelination of axons compared to controls. To further confirm the pro-myelinating function of IGFBP2, lysolecithin-induced rat model of focal demyelination was used. Our results showed that IGFBP2 treatment was sufficient to attenuate anxiety-like behaviors and promote remyelination in lysolecithin-induced rat model of focal demyelination. In addition, the RS rats treated with IGFBP2 significant increase in the thickness and length of PSD.

Discussion & Conclusion
Collectively, our results demonstrate that the ultrastructural and functional changes of myelin and synaptic alterations in mPFC could be involved in stress-induced anxiety-like behavior. Notably, our study provides the first evidence that systemic delivery of IGFBP2 produced rapid-acting effects in rescuing the anxiety like behavior in RS rat models, which provides a critical rationale about IGFBP2 may has therapeutic potential for the treatment of anxiety disorders from a translational perspective clinically and deserves further study to provide more evidence for the treatment of anxiety disorder in the future.
THE LONGITUDINAL IMPACT OF COVID-19 LOCKDOWNS ON COGNITIVE FUNCTION IN INDIVIDUALS WITH ALZHEIMER’ S DISEASE AND MILD COGNITIVE IMPAIRMENT
Authors: Lee *Hahyun , Lee Jun-Young 
Published: February 2025

Abstract

Objective
This study aims to comprehensively assess the longitudinal repercussions of the COVID-19 lockdowns on individuals diagnosed with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI).

Methods
The study involved a cohort of 130 individuals (50 MCI, 80 AD) who underwent cognitive assessments in Korea from 2018 to 2021. Longitudinal data were collected to assess the impact of COVID-19 lockdowns. Linear mixed-effects models were employed to assess changes in cognitive, psychological, and behavioral functioning in people with MCI/AD. Path analysis was used to explore the relationships between various cognitive measures(MMSE, CERAD, ADL, IADL, SGDS, NPI) and the Clinical Dementia Rating Scale Sum of Boxes (CDR_SUM)

Results
The findings revealed a statistically significant decline in cognitive function among AD patients during the lockdown period. In contrast, individuals with MCI exhibited comparatively milder deterioration. In the path analysis, MMSE, ADL, and IADL exhibited strong negative associations with CDR_SUM, emphasizing their predictive value in determining the severity of clinical dementia.

Discussion & Conclusion
This study underscores the disproportionate vulnerability of AD individuals to the cognitive consequences of lockdown measures. Our findings highlight the profound impact of social isolation on cognitive functions in individuals with MCI and AD. The integration of linear mixed-effects models and path analysis offers a comprehensive understanding of the dynamic cognitive changes occurring over time. Future interventions and support systems should prioritize addressing specific cognitive domains, such as memory, activities of daily living, and instrumental activities of daily living, to effectively mitigate the adverse effects of social isolation on dementia progression.
ADMINISTRATION OF SSRI DURING PREGNANCY AFFECTED BEHAVIORAL CHANGES AND HIPPOCAMPAL NEUROGENESIS IN OFFSPRING IN RATS
Authors: Horie *Junko , Kinjo Tomoya , Ito Masanobu , Suzuki Toshihito 
Published: February 2025

Abstract

Background
Approximately 10 - 20 % pregnant women have been diagnosed with depression, and 3 - 6% pregnant women receive SSRI treatment. In Japan, it reported that approximately 1% of pregnant women (105 out of 10,000 births) were prescribed SSRIs during the perinatal period. Importantly, SSRIs crossed the placenta and may affect perinatal outcomes in infants exposed to these drugs during pregnancy in human. Several large cohort studies have been conducted, some finding significant differences in the risk of ASD and others not. In the present study, we created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure.

Aims & Objectives
We created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure in rats.

Methods
We used pregnant female Wistar rats. Paroxetine was administered daily from ED12.5 to ED21.5, covering the last 9–12 days of pregnancy. Oral sondes were used to keep rodents at a constant daily dose, and paroxetine 1 mg / kg / day or paroxetine 2.5 mg / kg / day or saline was given to the control group. The control group received saline daily. We evaluated spontaneous locomotor activity using the open field test (OF), spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze test (EPM) in male offspring at PD30. BrdU-positive cells in hippocampus were counted by fluorescence microscope.

Results
Locomotor activities significantly increase in paroxetine 2.5 mg group compare to a control group. The paroxetine 2.5 mg group spent less time in the closed arm compared to the control and paroxetine 1 mg groups in EPM. The number of BrdU-positive cells was significantly increased in the paroxetine 2.5 mg group compared to the control group. There was tendency to be a positive correlation between spontaneous activity and the number of BrdU-positive cells.

Discussion & Conclusions
In this study, it was revealed that oral administration of paroxetine during pregnancy induces hyperactivities and impulsivities in offspring, and increased neurogenesis in hippocampus of rats. There was a positive correlation between locomotor activity and the amount of neurogenesis. SSRI administration during pregnancy may affect the neurodevelopment of the newborn infant.
THE RECOVERY EFFECT OF STEM CELLS AND KAMPO MEDICINE KAMIKIHITO ON SOCIAL BEHAVIOR DYSFUNCTIONS IN REFRACTORY PSYCHIATRIC DISORDERS
Authors: Ukai *Wataru , Deriha Kenta , Nishimura Emi , Hashimoto Eri , Yamada Misa , Hashiguchi Hanako , Hirose Shoma , Mochizuki Marina , Momoki Yukihiko , Furuse Kengo , Ishii Takao , Nagaishi Kanna , Riva Marco A , Kawanishi Chiaki 
Published: February 2025

Abstract

Background
The brain pathophysiology of social dysfunctions in depression and autism spectrum disorder are complex, and there is a growing need to understand the relevant neuronal circuit alterations and to find direct and effective treatments for their recoveries.

Aims & Objectives
In this study, we have investigated the influences of bone marrow-derived mesenchymal stem cell (MSC) transplantation and Japanese Kampo medicine, Kamikihito on social behaviors as a novel treatment options for intractable psychiatric disorders, using refractory depression animal model related to stress vulnerability, we had preliminary established, induced by dual stress during embryonic/juvenile period (Furuse et al., 2019).

Method
We explored the possibility that MSC transplantation, which we have demonstrated the recovery effect on behavioral abnormalities in refractory depression model (Kigawa et al., 2014), and Kamikihito that has been used for anxiety and nervousness in clinics and recently reported to induce changes in emotional and social functions via oxytocinergic neuron enhancement (Tsukada et al., 2021), may promote neural repair and regeneration in brain regions related to social cognition and empathy, which in turn may enhance recovery for social dysfunctions.

Results
In the refractory depression model, active social interaction behavior, as indicated in the social interaction test, was reduced by approximately 50%. In contrast, treatments of MSC alone or MSC and kamikihito significantly improved social interaction behavior, which was reduced in the model animal. On the other hand, no such effects were observed in the group treated with kamikihito alone. In the model group, contact time with the restrained individual and empathy-like voluntary behavior as indicated by rescue behavior were reduced by approximately 40%. Interestingly, the reduction of empathy-like behavior in the model group was significantly improved in the groups treated with kamikihito alone and in the group treated with kamikihito and MSC. On the other hand, MSC monotreatment group could not show any effect.

Discussion & Conclusion
We would add some data of analyzing changes of dynamics of oxytocinergic neurons from the hypothalamic paraventricular nucleus, Parvalbumin (PV)/somatostatin (SS) positive GABA interneuron changes in brain regions including the cingulate cortex, amygdala, and hippocampus in each animal group, and identify brain circuit mutations that lead to social cognitive behavioral abnormalities for revealing the mechanisms of their recoveries.
VITAMIN D AND DEPRESSION
Authors: Suryani *Puji Rizki , Zulissetiana Eka Febri , Prananjaya Bintang Arroyantri , Aini Syarifah , Ikhsan Diyaz Syauki 
Published: February 2025

Abstract

Background
Depression is one of the mood disorders that is often found today. The cause of depression has not yet been determined, but it is believed that genetic, biological and psychosocial factors play an important role. One of them that was found was vitamin D deficiency.1 However, the effect of administering vitamin D in depressed patients has not been determined. Several studies have not found a link between giving vitamin D and improving patients depressive symptoms. Some studies show a positive relationship, but several other studies show a negative or even inconsistent relationship.2

Aims and Objective
This is the basis on which this research was conducted, to determine blood serotonin levels in mice treated with vitamin D.

Method
By using mice induced depression by immobilization, giving Fluoxetine as a standard drug used to treat depression and vitamin D as a comparison, serotonin levels in the mice's blood will be seen. Four groups were divided by the given treatment. No intervention in the first group, while the second group was given Fluoxetine, the third group was given vitamin D, and the last group was given Fluoxetine and vitamin D.

Results
The average serotonin levels in the four groups respectively are 0.031557 pg/ml, 0.031560 pg/ml, 0.031529 pg/ml, and 0.031614 pg/ml. Based on statistical analysis, there were no significant differences between the four groups.

Discussion and Conclusion
In this study, administration of vitamin D and Fluoxetine showed the highest serotonin levels. Fluoxetine is an antidepressant that is often used for depression. Vitamin D metabolites can penetrate the brain barrier and are believed to have an effect as neuroprotector. This may lead the suggests that it also has an effect on depressive symptoms.3A number of studies have found that single administration of vitamin D has an effect on depressive symptoms, while other studies have shown no effect. In this study, serotonin levels in the third group were the lowest which means it shows no effect on depression. 3It can be concluded that giving vitamin D does not have a significant effect on depressive symptoms.

References
Rebecca E S Anglin, Zainab Samaan, Stephen D Walter, Sarah D McDonald. 2018. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. https://pubmed.ncbi.nlm.nih.gov/23377209/. Guowei Li, Lawrence Mbuagbaw, Zainab Samaan et al. 2013. Efficacy of Vitamin D supplementation in depression in adults: a systematic review protocol. Biomed Central. http://ncbi.nlm.nih.gov. Vikas Menon,Sujita Kumar Kar, Navratan Suthar, and Naresh Nebhinani. 2020. Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions. Indian J Psychol Med. 42(1): 11–21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970300/
INVOLVEMENT OF PGE2-EP1 SIGNALING IN THE PTZ-INDUCED EPILEPTIC SEIZURE AND ITS NEUROINFLAMATION-ASSOCIATED EXACERBATION
Authors: Ishizaka *Yukino , Mouri Akihiro , Kunisawa Kazuo , Nishikawa Takaya , Furuyashiki Tomoyuki , Narumiya Shuh , Nabeshima Toshitaka 
Published: February 2025

Abstract

Background
Epilepsy is one of the most common neurological disorders. Neuroinflammation and an enhanced excitability via NMDA receptor are known to be involved in the pathophysiology of epilepsy. The cyclooxygenase (COX)/prostaglandin E2 (PGE2) signaling pathway plays a critical role in the neuroinflammation. Among PGE2 receptors (EP1-4), EP1 contributes to NMDA receptor-mediated neuronal excitability.

Aims & Objectives
We aimed to investigate whether the PGE2-EP1 signaling is involved in the epileptic seizures induced by pentylenetetrazol (PTZ) in mice.

Method
Pentylenetetrazol (PTZ) was administered to mice every other consecutive day and seizures were evaluated. Co-administration of lipopolysaccharide (LPS) with PTZ and seizure scores were evaluated. Brains were removed and PGE2-related gene mRNA was measured by real-time PCR.

Results
Chronic administration of PTZ exacerbated epileptic seizures and increased expression of EP1 but not cyclooxygenases (COXs) and microsomal prostaglandin E synthases (mPGESs). The exacerbation of seizure was attenuated in the EP1-knockout mice. Co-administration of lipopolysaccharide (LPS) with PTZ increased body-temperature associated with enhanced expression of COX-2 and mPGES-1 and exacerbated epileptic seizures. This exacerbated seizure was also attenuated in the EP1- knockout mice.

Discussion & Conclusion
These data suggested that PGE2-EP1 signaling may have critical roles in the pathophysiology of epilepsy and its exacerbation with neuroinflammation. In conclusion, EP1 receptors may be attractive therapeutic target for epileptic seizure.