BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus.
METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis.
RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice.
CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

This chapter aims to provide a comprehensive overview of the methodologies available to dissect genetic regulation of the nervous systems in the nematode Caenorhabditis elegans. These techniques encompass genetic screens and genetic tools to unravel the spatial-temporal contribution of genes on neural structure and function. Unbiased genetic screens on random mutations induced by ethyl methanesulfonate (EMS) or target gene silencing by genome-wide RNA interference (RNAi) help progress our understanding of the genetic control of neural development and functions. Complement to unbiased genetic approaches, gene- and protein-targeted manipulation by Cre/LoxP recombination system and auxin-inducible degron (AID) protein degradation system, respectively, helps identify tissues/cells and the time window critical for gene and protein function during the proper execution of a particular behavior. Considering the remarkable conservation of genetic pathways between C. elegans and mammalian systems, elucidating the genetic underpinnings of neural functions and learning behaviors in C. elegans may furnish invaluable insights into analogous processes in more complex organisms. As shown in the following chapter, leveraging these diverse methodologies enable researchers to elucidate the intricate network governing neural function and structure, laying the foundation for innovating strategies to ameliorate cognitive alterations.

Sleeping problems are prevalent among children and adolescents, often leading to frequent consultations with pediatricians. While cognitive-behavioral therapy has shown effectiveness, especially in the short term, there is a lack of globally endorsed guidelines for the use of pharmaceuticals or over-the-counter remedies in managing sleep onset insomnia. An expert panel of pediatric sleep specialists and chronobiologists met in October 2023 to develop practical recommendations for pediatricians on the management of sleep onset insomnia in typically developing children. When sleep onset insomnia is present in otherwise healthy children, the management should follow a stepwise approach. Practical sleep hygiene indications and adaptive bedtime routine, followed by behavioral therapies, must be the first step. When these measures are not effective, low-dose melatonin, administered 30-60 min before bedtime, might be helpful in children over 2 years old. Melatonin use should be monitored by pediatricians to evaluate the efficacy as well as the presence of adverse effects.    Conclusion: Low-dose melatonin is a useful strategy for managing sleep onset insomnia in healthy children who have not improved or have responded insufficiently to sleep hygiene and behavioral interventions.

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

Three systemic biological systems, i.e., the nervous, the immune, and the cardiovascular systems, form a mutually responsive and forward-acting tissue network to regulate acute and chronic cardiovascular function in health and disease. Two sub-circuits within the cardiovascular system have been described, the artery brain circuit (ABC) and the heart brain circuit (HBC), forming a large cardiovascular brain circuit (CBC). Likewise, the nervous system consists of the peripheral nervous system and the central nervous system with their functional distinct sensory and effector arms. Moreover, the immune system with its constituents, i.e., the innate and the adaptive immune systems, interact with the CBC and the nervous system at multiple levels. As understanding the structure and inner workings of the CBC gains momentum, it becomes evident that further research into the CBC may lead to unprecedented classes of therapies to treat cardiovascular diseases as multiple new biologically active molecules are being discovered that likely affect cardiovascular disease progression. Here, we weigh the merits of integrating these recent observations in cardiovascular neurobiology into previous views of cardiovascular disease pathogeneses. These considerations lead us to propose the Neuroimmune Cardiovascular Circuit Hypothesis.

Ischemic stroke is closely associated with gut microbiota dysbiosis and intestinal barrier dysfunction. Prebiotic intervention could modulate the intestinal microbiota, thus considered a practical strategy for neurological disorders. Puerariae Lobatae Radix-resistant starch (PLR-RS) is a potential novel prebiotic; however, its role in ischemic stroke remains unknown. This study aimed to clarify the effects and underlying mechanisms of PLR-RS in ischemic stroke. Middle cerebral artery occlusion surgery was performed to establish a model of ischemic stroke in rats. After gavage for 14 days, PLR-RS attenuated ischemic stroke-induced brain impairment and gut barrier dysfunction. Moreover, PLR-RS rescued gut microbiota dysbiosis and enriched Akkermansia and Bifidobacterium. We transplanted the fecal microbiota from PLR-RS-treated rats into rats with ischemic stroke and found that the brain and colon damage were also ameliorated. Notably, we found that PLR-RS promoted the gut microbiota to produce a higher level of melatonin. Intriguingly, exogenous gavage of melatonin attenuated ischemic stroke injury. In particular, melatonin attenuated brain impairment via a positive co-occurrence pattern in the intestinal microecology. Specific beneficial bacteria served as leaders or keystone species to promoted gut homeostasis, such as Enterobacter, Bacteroidales_S24-7_group, Prevotella_9, Ruminococcaceae and Lachnospiraceae. Thus, this new underlying mechanism could explain that the therapeutic efficacy of PLR-RS on ischemic stroke at least partly attributed to gut microbiota-derived melatonin. In summary, improving intestinal microecology by prebiotic intervention and melatonin supplementation in the gut were found to be effective therapies for ischemic stroke.

Animal behaviour regulation is a complex process involving many factors, and the nervous system is an essential factor in this process. In many species, pathogens can alter host behaviour by affecting the host\'s nervous system. An interesting example is that the silkworm shows enhanced locomotor behaviour after being infected with the nucleopolyhedrosis virus. In this study, we analysed the transcriptome of the silkworm brain at different time points after infection and found that various genes related to behaviour regulation changed after infection. In-depth analysis showed that the tyrosine hydroxylase gene might be a key candidate gene, and the content of dopamine, its downstream metabolite, increased significantly in the brain of silkworms infected with the virus. After the injection of tyrosine hydroxylase inhibitor into the infected silkworm, the dopamine content in the silkworm brain decreased and the locomotor behaviour caused by the virus was blocked successfully. These results confirm that tyrosine hydroxylase is involved in regulating enhanced locomotor behaviour after virus infection in silkworms. Furthermore, the tyrosine hydroxylase gene was specifically overexpressed in the brain of the silkworm, and the transgenic silkworm was enhanced in locomotor behaviour and foraging behaviour. These results suggest that the tyrosine hydroxylase gene plays a vital role in regulating insect behaviour.

Alcohol is often found in the blood of the deceased. To cover up the true cause of victim\'s death, postmortem instillation of alcohol occurs in some criminal cases. Explaining the finding of alcohol is extremely vital in forensic practice. This study aims to evaluate whether ethyl glucuronide (EtG) and ethyl sulfate (EtS) in blood and vitreous humor (VH) can be used to distinguish alcoholic death and postmortem alcohol instillation. Saline or 12.6 g/kg ethanol (antemortem alcohol poisoning group) was introduced into rabbits\' stomachs 2 h before sacrificed. Same amount of ethanol was introduced into rabbits\' stomachs at 0 h, 0.5 h, 1 h and 2 h after death in four subgroups of postmortem alcohol instillation group, respectively. Cardiac blood and VH were collected at 10 min, 4 h, 10 h and 24 h after death in blank and antemortem alcohol poisoning group, and after instillation of alcohol in postmortem alcohol instillation group. Blood was also collected at 34 h. Ethanol and EtG levels in blood and VH and EtS in VH in antemortem alcohol poisoning group were overlapped with those in postmortem alcohol instillation group. The contents of EtG and EtS in blood in antemortem alcohol poisoning group (mean ≥ 7.833 μg/mL for EtG and ≥ 19.990 μg/mL for EtS) were much higher than those in postmortem alcohol instillation group (mean ≤ 0.118 μg/mL for EtG and ≤ 0.091 μg/mL for EtS), but apparent decomposition was observed in EtG, which might lead to misinterpretation. Blood EtS showed better stability and could be used to distinguish alcoholic death and postmortem alcohol instillation.

Cerebellar Purkinje cells (PCs) play critical roles in motor coordination and motor learning through their simple spike (SS) activity. Previous studies have shown that chronic ethanol exposure (CEE) in adolescents impairs learning, attention, and behavior, at least in part by impairing the activity of cerebellar PCs. In this study, we investigated the effect of CEE on the SS activity in urethane-anesthetized adolescent mice by in vivo electrophysiological recordings and pharmacological methods. Our results showed that the cerebellar PCs in CEE adolescent mice expressed a significant decrease in the frequency and an increase in the coefficient of variation (CV) of SS than control group. Blockade of ɤ-aminobutyric acid A (GABAA) receptor did not change the frequency and CV of SS firing in control group but produced a significant increase in the frequency and a decrease in the CV of SS firing in CEE mice. The CEE-induced decrease in SS firing rate and increase in CV were abolished by application of an N-methyl-D-aspartate (NMDA) receptor blocker, D-APV, but not by anα-amino-3-hydroxy-5-methyl -4-isoxazolepropionic acid (AMPA) receptor antagonist, NBQX. Notably, the spontaneous spike rate of molecular layer interneurons (MLIs) in CEE mice was significantly higher than control group, which was also abolished by application of D-APV. These results indicate that adolescent CEE enhances the spontaneous spike firing rate of MLIs through activation of NMDA receptor, resulting in a depression in the SS activity of cerebellar PCs in vivo in mice.

Research on melatonin remains one of the major hot spots in the field of disease treatment, but relevant data are numerous. The purpose of this study was to quantitatively and qualitatively analyze the progress of melatonin research through the method of bibliometrics and to predict hot spots and trends in melatonin research. This study retrieved all the studies on melatonin from 2000 to 2019 in the Web of Science and PubMed and analysed the publishing trends in the literature on a bibliometric online analysis platform and CiteSpace software. The research results were also visually analysed to summarize melatonin research hot spots through gCLUTO and pubMR. The study retrieved a total of 20,351 publications, of which the number of US publications ranked first, accounting for 21.46%, with the greatest impact (centrality = 0.31). The University of Texas Health Science Center at San Antonio and Harvard University had the highest average number of citations at 43.19 and 33.96, respectively. Journal of Pineal Research had the highest average number of citations in 2,993 journals. Professor Reiter made the largest contribution to this area. We further analysed 100 highly cited articles for clinical applications and ongoing related clinical drug trials based on the first hot spot. We systematically analysed melatonin for nearly 20 years while predicting the main research trends in the future, which may provide new directions and ideas for melatonin research. The structure and normal physiological functions of melatonin have been intensively studied in the past few years. And clinical application research and target of melatonin treatment for different diseases and target-based drug design will certainly become the focus of melatonin research.