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International Journal of Molecular... Jun 2024It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral...
It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait ( < 0.0001) and neuroticism ( < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A ( < 0.0001) and G/G ( = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A ( < 0.0001) and G/G ( < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Female; Alcoholism; Adult; Polymorphism, Single Nucleotide; Personality; Middle Aged; Anxiety; Genetic Predisposition to Disease; Genotype; Neuroticism; Case-Control Studies
PubMed: 38928154
DOI: 10.3390/ijms25126448 -
Biology Jun 2024, as an invasive exotic species in Asia, can adversely affect crop yields, eco-environment, and human health. Application of molluscicides containing metaldehyde is one...
, as an invasive exotic species in Asia, can adversely affect crop yields, eco-environment, and human health. Application of molluscicides containing metaldehyde is one effective method for controlling . In order to investigate the effects of metaldehyde on adult snails, we conducted acute toxicological experiments to investigate the changes in enzyme activities and histopathology after 24 h and 48 h of metaldehyde action. The results showed that the median lethal concentrations (LC) of metaldehyde on were 3.792, 2.195, 1.833, and 1.706 mg/L at exposure times of 24, 48, 72, and 96 h, respectively. Treatment and time significantly affected acetylcholinesterase (AChE), glutathione S-transferase (GST), and total antioxidant capacity (TAC) activity, with sex significantly affecting AChE, GST, and TAC activity and time significantly affecting carboxylesterase (CarE). In addition, the interaction of treatment and time significantly affected the activity of GST, CarE and TAC. In addition, histopathological changes occurred in the digestive glands, gills and gastropods of apple snail exposed to metaldehyde. Histological examination of the digestive glands included atrophy of the digestive cells, widening of the hemolymph gap, and an increase in basophils. In treated snails, the hemolymph gap in the gills was widely dilated, the columnar cells were disorganized or even necrotic, and the columnar muscle cells in the ventral foot were loosely arranged and the muscle fibers reduced. The findings of this study can provide some references for controlling the toxicity mechanism of invasive species.
PubMed: 38927309
DOI: 10.3390/biology13060428 -
Behavioral and Brain Functions : BBF Jun 2024An intronic deletion within intron 2 of the DCDC2 gene encompassing the entire READ1 (hereafter, READ1d) has been associated in both children with developmental dyslexia...
BACKGROUND
An intronic deletion within intron 2 of the DCDC2 gene encompassing the entire READ1 (hereafter, READ1d) has been associated in both children with developmental dyslexia (DD) and typical readers (TRs), with interindividual variation in reading performance and motion perception as well as with structural and functional brain alterations. Visual motion perception -- specifically processed by the magnocellular (M) stream -- has been reported to be a solid and reliable endophenotype of DD. Hence, we predicted that READ1d should affect neural activations in brain regions sensitive to M stream demands as reading proficiency changes.
METHODS
We investigated neural activations during two M-eliciting fMRI visual tasks (full-field sinusoidal gratings controlled for spatial and temporal frequencies and luminance contrast, and sensitivity to motion coherence at 6%, 15% and 40% dot coherence levels) in four subject groups: children with DD with/without READ1d, and TRs with/without READ1d.
RESULTS
At the Bonferroni-corrected level of significance, reading skills showed a significant effect in the right polar frontal cortex during the full-field sinusoidal gratings-M task. Regardless of the presence/absence of the READ1d, subjects with poor reading proficiency showed hyperactivation in this region of interest (ROI) compared to subjects with better reading scores. Moreover, a significant interaction was found between READ1d and reading performance in the left frontal opercular area 4 during the 15% coherent motion sensitivity task. Among subjects with poor reading performance, neural activation in this ROI during this specific task was higher for subjects without READ1d than for READ1d carriers. The difference vanished as reading skills increased.
CONCLUSIONS
Our findings showed a READ1d-moderated genetic vulnerability to alterations in neural activation in the ventral attentive and salient networks during the processing of relevant stimuli in subjects with poor reading proficiency.
Topics: Humans; Dyslexia; Male; Child; Female; Magnetic Resonance Imaging; Parietal Lobe; Reading; Motion Perception; Frontal Lobe; Microtubule-Associated Proteins; Brain Mapping; Nerve Net; Photic Stimulation
PubMed: 38926731
DOI: 10.1186/s12993-024-00241-2 -
Scientific Reports Jun 2024Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a...
Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.
Topics: Humans; Hallucinations; Lewy Body Disease; Gray Matter; Female; White Matter; Male; Aged; Magnetic Resonance Imaging; Aged, 80 and over; Case-Control Studies; Middle Aged
PubMed: 38926597
DOI: 10.1038/s41598-024-65536-w -
Scientific Reports Jun 2024Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this...
Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus's central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew's auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.
Topics: Animals; Shrews; Superior Olivary Complex; Auditory Pathways; Neurons; Inferior Colliculi; Calcium-Binding Proteins; Brain Stem; Male; Olivary Nucleus
PubMed: 38926520
DOI: 10.1038/s41598-024-65451-0 -
Scientific Reports Jun 2024In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether...
In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5-6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P < 0.0001 and P = 0.015, respectively). However, the difference between the b-wave amplitudes elicited at D30° and V30° stimuli were not significant (P = 0.98), and the d-wave amplitudes were also not significantly different (P = 0.20). The average b-wave amplitudes elicited at D30° stimulation was 84.6 ± 15.7% and V30° stimulation was 84.8 ± 17.4% relative to that of F0° stimulation. The average d-wave amplitudes elicited by D30° stimulation was 85.5 ± 15.2% and by V30° stimulation was 79.0 ± 11.0% relative to that of F0° stimulation. The differences in the implicit times of the b- and d-wave elicited by the different directions of stimulation were not significant (P = 0.52 and P = 0.14, respectively). We conclude that the amplitude of the photopic ERGs is affected by the angle of the incident light. Thus, it would be better to use ganzfeld stimuli to elicit maximum b- and d-wave amplitudes of the photopic ERGs of zebrafish larvae.
Topics: Animals; Zebrafish; Electroretinography; Larva; Photic Stimulation; Light; Retina
PubMed: 38926421
DOI: 10.1038/s41598-024-65017-0 -
ENeuro Jun 2024Layer 6 corticothalamic (L6 CT) neurons provide massive input to the thalamus, and these feedback connections enable the cortex to influence its own sensory input by...
Layer 6 corticothalamic (L6 CT) neurons provide massive input to the thalamus, and these feedback connections enable the cortex to influence its own sensory input by modulating thalamic excitability. However, the functional role(s) feedback serves during sensory processing is unclear. One hypothesis is that CT feedback is under the control of extra-sensory signals originating from higher-order cortical areas, yet we know nothing about the mechanisms of such control. It is also unclear whether such regulation is specific to CT neurons with distinct thalamic connectivity. Using mice (either sex) combined with in vitro electrophysiology techniques, optogenetics, and retrograde labeling, we describe studies of vibrissal primary motor cortex (vM1) influences on different CT neurons in the vibrissal primary somatosensory cortex (vS1) with distinct intrathalamic axonal projections. We found that vM1 inputs are highly selective, evoking stronger postsynaptic responses in Dual ventral posterior medial nucleus (VPm) and posterior medial nucleus (POm) projecting CT neurons located in lower L6a than VPm-only projecting CT cells in upper L6a. A targeted analysis of the specific cells and synapses involved revealed that the greater responsiveness of Dual CT neurons was due to their distinctive intrinsic membrane properties and synaptic mechanisms. These data demonstrate that vS1 has at least two discrete L6 CT subcircuits distinguished by their thalamic projection patterns, intrinsic physiology, and functional connectivity with vM1. Our results also provide insights into how a distinct CT subcircuit may serve specialized roles specific to contextual modulation of tactile-related sensory signals in the somatosensory thalamus during active vibrissa movements. Layer 6 corticothalamic (L6 CT) feedback circuits are ubiquitous across mammalian species and modalities, and their activities have a strong influence on thalamic excitability and information throughput to the neocortex. Despite clear evidence of CT effects on the thalamus, we know relatively little about how CT cells themselves are regulated. Our results show that input from the primary motor cortex strongly excites a subclass of CT neurons in the primary somatosensory cortex that innervate both core and higher-order somatosensory nuclei rather than those exclusively targeting core somatosensory thalamus. The cortico-cortico-thalamic pathway formed by these connections establishes a circuit-level substrate for supporting CT influence operating under the guidance of ongoing motor activities.
PubMed: 38926084
DOI: 10.1523/ENEURO.0255-24.2024 -
Cell Reports Jun 2024Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current...
Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SC). SC forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
PubMed: 38923461
DOI: 10.1016/j.celrep.2024.114383 -
Veterinary Sciences Jun 2024A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two...
A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two months and died suddenly during a leashed walk. Upon necropsy, enlargement of the submandibular, prescapular, and popliteal lymph nodes was noted. The intrathoracic cavity contained a substantial volume of yellowish-white fluid. Lymph nodes in the mediastinal and ventral thoracic centers were also enlarged, hemorrhagic, and friable. Microscopic examination revealed significant architectural changes in the lymph nodes, characterized by a pronounced cellular infiltrate consisting of lymphocytes and histiocytes, along with macrophages containing intracytoplasmic amastigotes. Immunohistochemical analysis of the lymph nodes confirmed positive staining for amastigotes. This case represents the first report of canine leishmaniasis associated with acute pleural effusion and sudden death.
PubMed: 38922000
DOI: 10.3390/vetsci11060254 -
Cells Jun 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has increasingly linked the activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome to ALS pathogenesis. NLRP3 activation triggers Caspase 1 (CASP 1) auto-activation, leading to the cleavage of Gasdermin D (GSDMD) and pore formation on the cellular membrane. This process facilitates cytokine secretion and ultimately results in pyroptotic cell death, highlighting the complex interplay of inflammation and neurodegeneration in ALS. This study aimed to characterize the NLRP3 inflammasome components and their colocalization with cellular markers using the wobbler mouse as an ALS animal model. Firstly, we checked the levels of miR-223-3p because of its association with NLRP3 inflammasome activity. The wobbler mice showed an increased expression of miR-223-3p in the ventral horn, spinal cord, and cerebellum tissues. Next, increased levels of NLRP3, pro-CASP 1, cleaved CASP 1 (c-CASP 1), full-length GSDMD, and cleaved GDSMD revealed NLRP3 inflammasome activation in wobbler spinal cords, but not in the cerebellum. Furthermore, we investigated the colocalization of the aforementioned proteins with neurons, microglia, and astrocyte markers in the spinal cord tissue. Evidently, the wobbler mice displayed microgliosis, astrogliosis, and motor neuron degeneration in this tissue. Additionally, we showed the upregulation of protein levels and the colocalization of NLRP3, c-CASP1, and GSDMD in neurons, as well as in microglia and astrocytes. Overall, this study demonstrated the involvement of NLRP3 inflammasome activation and pyroptotic cell death in the spinal cord tissue of wobbler mice, which could further exacerbate the motor neuron degeneration and neuroinflammation in this ALS mouse model.
Topics: Animals; Amyotrophic Lateral Sclerosis; NLR Family, Pyrin Domain-Containing 3 Protein; Motor Neurons; Inflammasomes; Mice; MicroRNAs; Spinal Cord; Disease Models, Animal; Nerve Degeneration; Microglia; Mice, Inbred C57BL; Caspase 1
PubMed: 38920626
DOI: 10.3390/cells13120995