Alcohol tolerance is a neuroadaptive response that leads to a reduction in the effects of alcohol caused by previous exposure. Tolerance plays a critical role in the development of alcohol use disorder (AUD) because it leads to the escalation of drinking and dependence. Understanding the molecular mechanisms underlying alcohol tolerance is therefore important for the development of effective therapeutics and for understanding addiction in general. This review explores the molecular basis of alcohol tolerance in invertebrate models, Drosophila and C. elegans, focusing on synaptic transmission. Both organisms exhibit biphasic responses to ethanol and develop tolerance similar to that of mammals. Furthermore, the availability of several genetic tools makes them a great candidate to study the molecular basis of ethanol response. Studies in invertebrate models show that tolerance involves conserved changes in the neurotransmitter systems, ion channels, and synaptic proteins. These neuroadaptive changes lead to a change in neuronal excitability, most likely to compensate for the enhanced inhibition by ethanol.

Aging is characterized by the decline in many of the individual\'s capabilities. It has been recognized that the brain undergoes structural and functional changes during aging that are occasionally associated with the development of neurodegenerative diseases. In this sense, altered glutamatergic neurotransmission, which involves the release, binding, reuptake, and degradation of glutamate (Glu) in the brain, has been widely studied in physiological and pathophysiological aging. In particular, changes in glutamatergic neurotransmission are exacerbated during neurodegenerative diseases and are associated with cognitive impairment, characterized by difficulties in memory, learning, concentration, and decision-making. Thus, in the present manuscript, we aim to highlight the relevance of glutamatergic neurotransmission during cognitive impairment to develop novel strategies to prevent, ameliorate, or delay cognitive decline. To achieve this goal, we provide a comprehensive review of the changes reported in glutamatergic neurotransmission components, such as Glu transporters and receptors during physiological aging and in the most studied neurodegenerative diseases. Finally, we describe the current therapeutic strategies developed to target glutamatergic neurotransmission.

The present investigation explored the potential neuroprotective role of zinc oxide nanoparticles (ZnONPs) on aluminum chloride (AlCl3)-mediated Alzheimer\'s disease (AD)-like symptoms. Rats were distributed into four treatment groups equally: control, ZnONPs (4 mg/kg b.wt.), AlCl3 (100 mg/kg b.wt.), and ZnONPs + AlCl3 groups. Rats were treated for 42 consecutive days. ZnONPs injection into AlCl3-treated rats suppressed the development of oxidative challenge in the cortical and hippocampal tissues, as demonstrated by the decreased neuronal pro-oxidants (malondialdehyde and nitric oxide), and the increased glutathione and catalase levels. Additionally, ZnONPs injection showed anti-inflammatory potency in response to AlCl3 by decreasing levels of tumor necrosis factor-α and interleukin-1β. Moreover, pretreatment with ZnONPs prevented neuronal cell loss by decreasing the level of pro-apoptotic caspase-3 and enhancing the anti-apoptotic B cell lymphoma 2. Furthermore, ZnONPs ameliorated the disturbed acetylcholinesterase activity, monoamines (norepinephrine, dopamine, and serotonin), excitatory (glutamic and aspartic acids), and inhibitory amino acids (GABA and glycine) in response to AlCl3 exposure. These findings indicate that ZnONPs may have the potential as an alternative therapy to minimize or prevent the neurological deficits in AD model by exhibiting antioxidative, anti-inflammation, anti-apoptosis, and neuromodulatory effects.

OBJECTIVE: To evaluate for associations between the occurrence of palpitations reported by women prior to breast cancer surgery and single nucleotide polymorphisms (SNPs) for neurotransmitter genes.
UNASSIGNED: A total of 398 women, who were scheduled for unilateral breast cancer surgery, provided detailed information on demographic and clinical characteristics and the occurrence of palpitations prior to breast cancer surgery.
UNASSIGNED: The occurrence of palpitations was assessed using a single item (i.e., \"heart races/pounds\" in the past week [\"yes\"/\"no\"]). Blood samples were collected for genomic analyses. Multiple logistic regression analyses were used to identify associations between the occurrence of palpitations and variations in neurotransmitter genes.
RESULTS: Nine SNPs and two haplotypes among 11 candidate genes were associated with the occurrence of palpitations. These genes encode for a number of neurotransmitters and/or their receptors, including serotonin, norepinephrine, dopamine, gamma-amino butyric acid, Substance P, and neurokinin.
CONCLUSIONS: These findings suggest that alterations in a variety of neurotransmitters contribute to the development of this symptom.

This review critically examines the contributions of pupillometry to memory research, primarily focusing on its enhancement of our understanding of memory encoding and retrieval mechanisms mainly investigated with the recognition memory paradigm. The evidence supports a close link between pupil response and memory formation, notably influenced by the type of novelty detected. This proposal reconciles inconsistencies in the literature regarding pupil response patterns that may predict successful memory formation, and highlights important implications for encoding mechanisms. The review also discusses the pupil old/new effect and its significance in the context of recollection and in reflecting brain signals related to familiarity or novelty detection. Additionally, the capacity of pupil response to serve as a true memory signal and to distinguish between true and false memories is evaluated. The evidence provides insights into the nature of false memories and offers a novel understanding of the cognitive mechanisms involved in memory distortions. When integrated with rigorous experimental design, pupillometry can significantly refine theoretical models of memory encoding and retrieval. Furthermore, combining pupillometry with neuroimaging and pharmacological interventions is identified as a promising direction for future research.

BACKGROUND: The nervous system is central to coordinating behavioural responses to environmental change, likely including ocean acidification (OA). However, a clear understanding of neurobiological responses to OA is lacking, especially for marine invertebrates.
RESULTS: We evaluated the transcriptomic response of the central nervous system (CNS) and eyes of the two-toned pygmy squid (Idiosepius pygmaeus) to OA conditions, using a de novo transcriptome assembly created with long read PacBio ISO-sequencing data. We then correlated patterns of gene expression with CO2 treatment levels and OA-affected behaviours in the same individuals. OA induced transcriptomic responses within the nervous system related to various different types of neurotransmission, neuroplasticity, immune function and oxidative stress. These molecular changes may contribute to OA-induced behavioural changes, as suggested by correlations among gene expression profiles, CO2 treatment and OA-affected behaviours.
CONCLUSIONS: This study provides the first molecular insights into the neurobiological effects of OA on a cephalopod and correlates molecular changes with whole animal behavioural responses, helping to bridge the gaps in our knowledge between environmental change and animal responses.

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Tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel additive brominated flame retardant, is being developed for use in polyolefin and copolymers. Despite its emerging application, the neurotoxicity and mechanisms of action of TBBPA-BDBPE remain unexplored. Caenorhabditis elegans was utilized as the model organism to study the neurotoxic effects of TBBPA-BDBPE across environmental concentrations ranging from 0 to 100 μg/L. This investigation focused on various toxicological endpoints such as locomotive behavior, neuronal injury, neurotransmitter transmission, and the regulation of nervous system-related gene expression. Acute exposure to TBBPA-BDBPE at concentrations of 10-100 μg/L significantly impaired nematode movement, indicating potential neurotoxicity. In transgenic nematodes, this exposure also caused damage to γ-aminobutyric acid (GABAergic) and serotonergic neurons, along with notable changes in the levels of GABAergic and serotonergic neurotransmitters. Further molecular studies indicated alterations in neurotransmission-related genes (cat-4, mod-1, unc-25, and unc-47). Molecular docking analysis confirmed the binding affinity of TBBPA-BDBPE to key neurotransmission proteins-CAT-4, MOD-1, UNC-25, and UNC-47. These findings demonstrate that TBBPA-BDBPE exerts neurotoxic effects by impacting GABAergic and serotonergic neurotransmission in nematodes. This study provides new insights into the potential environmental risks of TBBPA-BDBPE.

BACKGROUND: Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI.
METHODS: The \"Boolean logic\" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar.
RESULTS: Lithium\'s therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor-mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short- as well as long-term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo-cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI.
CONCLUSIONS: Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI.

Alzheimer\'s Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and cognitive decline. Healthy synapses are the crucial for normal brain function, memory restoration and other neurophysiological function. Synapse loss and synaptic dysfunction are two primary events that occur during AD initiation. Synapse lifecycle and/or synapse turnover is divided into five key stages and several sub-stages such as synapse formation, synapse assembly, synapse maturation, synapse transmission and synapse termination. In normal state, the synapse turnover is regulated by various biological and molecular factors for a healthy neurotransmission. In AD, the different stages of synapse turnover are affected by AD-related toxic proteins. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and have been implicated in various neurological diseases, including AD. Deregulation of miRNAs modulate the synaptic proteins and affect the synapse turnover at different stages. In this review, we discussed the key milestones of synapse turnover and how they are affected in AD. Further, we discussed the involvement of miRNAs in synaptic turnover, focusing specifically on their role in AD pathogenesis. We also emphasized the regulatory mechanisms by which miRNAs modulate the synaptic turnover stages in AD. Current studies will help to understand the synaptic life-cycle and role of miRNAs in each stage that is deregulated in AD, further allowing for a better understanding of the pathogenesis of devastating disease.