Accurate analysis of anxiety behaviors in animal models is pivotal for advancing neuroscience research and drug discovery. This study compares the potential of DeepLabCut, ZebraLab, and machine learning models to analyze anxiety-related behaviors in adult zebrafish. Using a dataset comprising video recordings of unstressed and pre-stressed zebrafish, we extracted features such as total inactivity duration/immobility, time spent at the bottom, time spent at the top and turn angles (large and small). We observed that the data obtained using DeepLabCut and ZebraLab were highly correlated. Using this data, we annotated behaviors as anxious and not anxious and trained several machine learning models, including Logistic Regression, Decision Tree, K-Nearest Neighbours (KNN), Random Forests, Naive Bayes Classifiers, and Support Vector Machines (SVMs). The effectiveness of these machine learning models was validated and tested on independent datasets. We found that some machine learning models, such as Decision Tree and Random Forests, performed excellently to differentiate between anxious and non-anxious behaviour, even in the control group, where the differences between subjects were more subtle. Our findings show that upcoming technologies, such as machine learning models, are able to effectively and accurately analyze anxiety behaviours in zebrafish and provide a cost-effective method to analyze animal behaviour.

This review explores the significant roles of neurotransmitters, focusing on dopamine and serotonin, in inflammation and cancer. These neurotransmitters are vital for neural signaling and play crucial roles in various physiological and pathological processes. We conducted an extensive literature review, focusing on studies published between 2013 and 2024, using databases such as PubMed, Google Scholar, and Scopus. Studies were selected based on relevance to neurotransmitter synthesis, receptor function, and their involvement in diseases like cancer and neurodegenerative disorders. The key search terms included "dopamine", "serotonin", "inflammation", and "cancer". Dopamine and serotonin are synthesized intracellularly and function as pivotal signaling molecules within the central nervous system (CNS) and peripheral systems. Through their respective receptors, dopamine and serotonin influence immune responses and the functionality of various bodily systems. Dysregulation in their signaling pathways is associated with a range of cancers and imbalances within the immune system. The interplay between dopamine and serotonin systems extends beyond neural communication, significantly affecting immune responses and inflammation. Dopamine's role in modulating immune cell activity highlights its potential in treating inflammatory conditions and cancer. Similarly, serotonin's extensive physiological impact underscores the importance of targeting 5-HT pathways in various disorders. Future research should focus on developing therapeutic strategies that leverage these neurotransmitters' regulatory functions in both the CNS and peripheral systems.

Parkinson's disease (PD) is primarily driven by the protein Alpha Synuclein (A-Syn) accumulation. Synphilin-1 protein, encoded by the SNCAIP gene, which co-localizes with A-Syn is a known risk factor for PD. Retinitis pigmentosa (RP), is a cluster of retinal degenerative disorders, and Cyclic Nucleotide Gated channel subunit Alpha 1 (CNGA1) is one of the initial genes associated with RP. Patients with PD can have various kinds of visual dysfunction as a non-motor manifestation, but to date, CNGA1 mutation and RP as a PD associated visual symptom has not been reported. We report a mutation in the SNCAIP gene in a PD patient, not reported earlier, and its co-occurrence with RP-associated CNGA1 gene mutation. Whole exome sequencing (WES) of the patient DNA sample and In-silico protein-protein interaction (PPI) analysis performed to find out proteins interacting with SNCAIP relevant concerning reported mutation of SNCAIP and further, CNGA1 interaction with SNCAIP. We are reporting, a missense mutation (p.Thr64Ser) at the SNCAIP gene, co-occurring with a missense variation (p.Gly509Arg) in the CNGA1 gene. In silico PPI analysis suggests SIAH1 as an important protein affected by SNCAIP mutation. LGALS4 and SNCA (gene encoding A-Syn) are common interactors between SNCAIP and CNGA1. The current study has determined the co-occurrence of RP and PD, whole exome sequencing ascertains the mutations in SNCAIP and CNGA1 genes, which could be the cause of PD and RP co-occurrence.

Loneliness is intricately connected to social cognition, yet the precise brain mechanisms that underscore their relationship need further exploration. The present study employed a theory of mind processing task that engaged participants in assessing the trajectories of geometric shapes while undergoing fMRI scans. The comprehensive data pool encompassed loneliness assessments and brain imaging data from a cohort of 157 participants. Utilizing a machine learning approach, task-induced functional connectivity data was used to forecast individuals' loneliness scores. The findings unveil that specific patterns of task-induced alterations in brain functional connectivity hold a remarkable capability to anticipate loneliness scores. Further dissection of the data disclosed pivotal nodes, including the prefrontal cortex, temporoparietal junction, and amygdala, among other cerebral regions. Furthermore, functional connectivity among the social network, the default mode network, and somatomotor networks emerged as crucial factors in prediction. Brain regions contributed strongly in prediction are involved in a variety of social cognitive processes, including intention inference, empathy, and information integration. The results illuminate the association between brain functional connectivity induced by social cognition and loneliness, which enhance the comprehensive understanding of this complex emotional state and may have implications for its diagnosis and intervention.

Infectious diseases are often concomitant with symptoms of lassitude and emotional disturbances, including depression, the so-called sickness behavior. Kososan, a Kampo (traditional Japanese herbal) formula, has been clinically used for depressive mood, with demonstrated efficacy in stress-induced depressive-like behavior mouse models. Additionally, our previous study has shown that nobiletin-rich kososan (NKS) prevents aging-related depressive-like behaviors and neuroinflammation in mice. Here, we examined whether NKS alleviates depressive-like behavior and neuroinflammation in a mouse model of sickness behavior induced by lipopolysaccharide (LPS). Repeated oral administration of NKS and the positive control antidepressant paroxetine (Paro) significantly prevented this behavior. NKS and Paro significantly increased the anti-inflammatory milieu in the hippocampus and prefrontal cortex (PFC), as well as brain microglia, of LPS-injected mice. The expression of the vascular tight junction protein claudin-5 was also significantly increased by the treatment with NKS, but not with Paro, in the hippocampus and PFC of LPS-injected mice. In vitro analysis using brain microvascular endothelial cells (BMVECs) showed that incubation with 5% serum derived from mice orally administered NKS resulted in a significant increase in the expression of anti-inflammatory heme oxygenase 1 as well as autophagic flux markers. Moreover, the claudin-5 levels in BMVECs were also increased under LPS-stimulated conditions. These results suggest that NKS exerts prophylactic effects against the LPS-induced apathy-like behavior, partly mediated by the increase in the anti-inflammatory milieu and in the levels of tight junction proteins in the brain. This study provides scientific evidence supporting the potential efficacy of NKS in preventing post-infection depression.

The conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is related to various factors. The causal relationships among these factors remain unclear. This study aims to investigate pathways of the progression by using causal analysis and build a predictive model with high accuracy. 162 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database. 68 patients progressed to AD. 94 patients did not convert to AD. We captured standard T1-weighted images, processed them for feature extraction, and selected relevant features using mRMR and LASSO to calculate cortical and nuclear scores. The computational causal structure discovery and regression analyses were adopted to analyze the intricate relationships among APOE ε4 alleles, P-tau, Aβ1-42, cortical and nuclear scores. The individualized prediction nomogram was constructed. Our results indicated that APOE ε4 alleles was the promoter that caused MCI to transform into AD. Three independent pathways were identified, including P-tau, Aβ1-42, and cortical atrophy. P-tau was the cause of nuclear atrophy. The APOE ε4 alleles, P-tau, Aβ1-42, cortical and nuclear scores all had good predictive value for the MCI conversion. The predictive accuracy of the combined model was the highest, with an AUC of 0.918 in the training cohort and 0.908 in the testing cohort. A multi-predictor nomogram was established. Our study elucidated the initiating factors and three independent pathways involved in the conversion of MCI to AD. The predictive value of each factor was clarified and a multi-predictor nomogram was established with high accuracy.

Traumatic brain injury is a prevalent condition that affects millions worldwide with no clear understanding or effective therapeutic management available. Military soldiers have a high risk of exposure to blast-induced traumatic brain injury (bTBI). Furthermore, alcohol drinking is common in this population, and studies have shown that post-TBI alcohol exposure can result in memory loss. Hence, it is possible that alcohol could contribute to the overall pathological outcome of brain trauma. However, such a possibility has not been explored in detail. Here, we combined a mild bTBI (mbTBI) model with the drinking-in-the-dark (DID) paradigm to investigate the pathological synergy between mbTBI and alcohol consumption by examining brain oxidative stress levels and behavioral alterations in mice. The results revealed the anxiolytic and short-term memory improvement effects of post-trauma alcohol drinking examined at an early timepoint post mbTBI. However, extended alcohol drinking for up to three weeks post mbTBI impaired long-term memory and was accompanied by intensified oxidative stress in brain regions associated with memory and anxiety. These findings, as well as those from previous in vitro TBI/alcohol studies, suggest a pathological synergy of physical force and post-impact alcohol exposure. This knowledge could potentially aid in establishing guidelines for TBI victims to avoid further injury to their brains as well as to help maximize their recovery following TBI.

Microglia polarization plays a crucial role in inflammatory injury of brain following intracerebral hemorrhage (ICH). Heme oxygenase-1 (HO-1) has demonstrated protective properties against inflammation and promote hematoma clearance after ICH. The objective of this study was to explore impacts of HO-1 on microglia polarization and phagocytosis after ICH, along with the underlying mechanism. ICH model was constructed in C57BL/6 mice. Neurological deficit of ICH mice was evaluated. HE detected pathological changes of mouse brain tissue. Immunofluorescence staining tested co-localization between HO-1 or NF-kB p65 and IBA1. The expressions of gene and proteins were detected by RT-qPCR and Western blot, respectively. Flow cytometry determined microglial polarization phenotype and neuron apoptosis. Cell viability of neuron was assessed by CCK-8. Red blood cells labeled by PKH-26 and co-cultured with microglia for examining microglial erythrophagocytosis. Both HO-1 and NF-kB p65 phosphorylation were elevated in brain tissues of ICH mice. ZnPP, a HO-1 inhibitor, could exacerbate microglial M1 polarization and nerve injury, as well as repress microglial erythrophagocytosis in vitro and hematoma clearance in vivo. On the contrary, Tat-NBD, a NF-kB inhibitor, greatly suppressed microglial M1 polarization, and induced M2 polarization and microglial erythrophagocytosis, thus improving nerve injury and hematoma clearance after ICH. Notably, it was observed that NF-kB p65 could be activated by ZnPP treatment, and the regulatory roles of ZnPP on microglial polarization and erythrophagocytosis after ICH in vivo and in vitro were all diminished by Tat-NBD. Therefore, our data demonstrated that HO-1 alleviated nerve injury and induced M2 polarization and phagocytosis of microglia after ICH via inhibiting NF-κB signaling pathway, which could provide deepen the pathological understanding of ICH and provide potential intervention targets and drug candidate for ICH.

In the last years, there has been a growing interest in the brain–heart connection. A core aspect of this connection appears to be the autonomic nervous system, particularly through the vagus nerve. Accordingly, vagally mediated heart rate variability (vmHRV) is currently considered as an index of top-down control processes involved in cognition and emotion regulation. Recent evidence indicates that higher vmHRV is associated with enhanced cognitive performance across multiple domains, such as executive functions, memory, attention, and language skills.From this premises, this study examined the relationship between cardiac vagal tone, as indicated by heart rate variability (vmHRV), and cognitive functions. A sample of 143 healthy young adults completed a comprehensive neuropsychological battery. The results revealed a strong correlation between resting vmHRV and cognitive functions, particularly in executive processes. Participants with higher resting vagal tone showed superior cognitive performance in tasks requiring cognitive control, motor and cognitive inhibition, cognitive flexibility, and working memory in comparison to those with lower resting vagal tone. Furthermore, vagal-mediated heart rate variability was also found to be associated with memory, attention, and executive performance. The current research provides new insights into the interactions between cognitive and autonomic systems, further supporting evidence for body-brain interactions.