Alterations In Neurotransmission Research Articles

Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalisation. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the last two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.

HiPSC-derived 3D neural models reveal neurodevelopmental pathomechanisms of the Cockayne Syndrome B

Cockayne Syndrome B (CSB) is a hereditary multiorgan syndrome which—through largely unknown mechanisms—can affect the brain where it clinically presents with microcephaly, intellectual disability and demyelination. Using human induced pluripotent stem cell (hiPSC)-derived neural 3D models generated from CSB patient-derived and isogenic control lines, we here provide explanations for these three major neuropathological phenotypes. In our models, CSB deficiency is associated with (i) impaired cellular migration due to defective autophagy as an explanation for clinical microcephaly; (ii) altered neuronal network functionality and neurotransmitter GABA levels, which is suggestive of a disturbed GABA switch that likely impairs brain circuit formation and ultimately causes intellectual disability; and (iii) impaired oligodendrocyte maturation as a possible cause of the demyelination observed in children with CSB. Of note, the impaired migration and oligodendrocyte maturation could both be partially rescued by pharmacological HDAC inhibition.Graphical

Alterations in neurotransmitters, steroid hormones, vitellogenin, and antioxidant system induced by di-n-butyl phthalate and di-isopentyl phthalate on catfish Rhamdia quelen.

Phthalates, such as di-n-butyl phthalate (DBP) and di-isopentyl phthalate (DiPeP), are pollutants with a high potential for endocrine disruption. This study aimed to evaluate parameters of endocrine disruption in specimens of the Neotropical fish Rhamdia quelen exposed to DBP and DiPeP through their food. After 30days of exposure, the fish were anesthetized and then euthanized, and blood, hypothalamus, liver, and gonads were collected. DBP caused statistically significant alterations in the serotoninergic system of males (5 and 25ng/g) and females (5ng/g) of R. quelen and it increased testosterone levels in females (25ng/g). DiPeP significantly altered the dopaminergic system in females, reduced plasma estradiol levels (125ng/g) and hepatic vitellogenin expression (25ng/g), and changed the antioxidant system in gonads (125ng/g). The results suggest that DBP and DiPeP may have different response patterns in females, with the former being androgenic and the latter being anti-estrogenic. These findings provide additional evidence regarding the molecular events involving DBP and DiPeP in the endocrine disruption potential in juvenile specimens of Rhamdia quelen.

Neuromuscular dysfunction and pathogenesis in triosephosphate isomerase deficiency

Triosephosphate isomerase deficiency (TPI Df) is a rare multisystem disorder with severe neuromuscular symptoms which arises exclusively from mutations within the TPI1 gene. Studies of TPI Df have been limited due to the absence of mammalian disease models and difficulties obtaining patient samples. Recently, we developed a novel murine model of TPI Df which models the most common disease-causing mutation in humans, TPI1E105D. Using our model in the present study, the underlying pathogenesis of neuromuscular symptoms has been elucidated. This is the first report detailing studies of neuromuscular pathology within a murine model of TPI Df. We identified several contributors to neuromuscular symptoms, including neurodegeneration in the brain, alterations in neurotransmission at the neuromuscular junction, and reduced muscle fiber size. TPI Df mice also exhibited signs of cardiac pathology and displayed a deficit in vascular smooth muscle functionality. Together, these findings provide insight into pathogenesis of the neuromuscular symptoms in TPI Df and can guide the future development of therapeutics.

Applying Spatial Metabolomics To Investigate Age- and Drug-Induced Neurochemical Changes.

In an era when population aging is increasing the burden of neurodegenerative conditions, deciphering the mechanisms underlying brain senescence is more important than ever. Here, we present a spatial metabolomics analysis of age-induced neurochemical alterations in the mouse brain using negative ionization mode mass spectrometry imaging. The age-dependent effects of the acetylcholinesterase inhibitor tacrine were simultaneously examined. For ultrahigh mass resolution analysis, we utilized a Fourier-transform ion cyclotron resonance spectrometer. To complement this, a trapped ion mobility spectrometry time-of-flight analyzer provided high speed and lateral resolution. The chosen approach facilitated the detection and identification of a wide range of metabolites, from amino acids to sphingolipids. We reported significant, age-dependent alterations in brain lipids which were most evident for sulfatides and lysophosphatidic acids. Sulfatide species, which are mainly localized to white matter, either increased or decreased with age, depending on the carbon chain length and hydroxylation stage. Lysophosphatidic acids were found to decrease with age in the detailed cortical and hippocampal subregions. An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.

Oral Neuropathy Associated with Commonly used Chemotherapeutic Agents: A Narrative Review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent complication of cytotoxic chemotherapeutic agents; its incidence largely varies, depending on type, dose, agent and preexisting risk factors. Oral-and-perioral-CIPN (OCIPN) is underreported. Neurotoxic agents can cause jaw pain or numbness. This review aims to present available data on OCIPN RECENT FINDINGS: A narrative literature review, following SANRA guidelines was conducted. PubMed and Cochrane databases were searched until September 2023. Articles referring to neuropathy or neuropathic pain due to head and neck cancer, head and neck radiotherapy, oropharyngeal mucositis, infection or post-surgical pain were excluded. Platinum-based chemotherapeutics, taxanes, vinca alkaloids, immunomodulatory and alkylating agents can cause OCIPN. Platinum-based chemotherapeutics can cause orofacial cold sensitivity, orofacial and jaw pain, oral cavity tingling and teeth hypersensitivity. Taxanes may induce oral cavity and tongue numbness and tingling as well as hot hypersensitivity. Vinca alkaloids may cause jaw, teeth and lips pain and oral mucosa hyperalgesia. Immunomodulatory drugs can cause lips, tongue and perioral numbness, while alkylating agents induce tongue and lips tingling and teeth cold-hypersensitivity. Chemotherapy may cause OCIPN due to changes in cellular structure and function, like alterations in membrane receptors and neurotransmission. OCIPN should be documented and physicians, dentists and health care providers should be alerted.

Combined non-targeted and targeted metabolomics reveals the mechanism of delaying aging of Ginseng fibrous root.

Background: The fibrous root of ginseng (GFR) is the dried thin branch root or whisker root of Ginseng (Panax ginseng C. A. Mey). It is known for its properties such as tonifying qi, producing body fluid, and quenching thirst. Clinically, it is used to treat conditions such as cough, hemoptysis, thirst, stomach deficiency, and vomiting. While GFR and Ginseng share similar metabolites, they differ in their metabolites ratios and efficacy. Furthermore, the specific role of GFR in protecting the body remains unclear. Methods: We employed ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to examine alterations in brain neurotransmitters and elucidate the impact of GFR on the central nervous system. Additionally, we analyzed the serum and brain metabolic profiles of rats using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry to discern the effect and underlying mechanism of GFR in delaying aging in naturally aged rats. Results: The findings of the serum biochemical indicators indicate that the intervention of GFR can enhance cardiovascular, oxidative stress, and energy metabolism related indicators in naturally aging rats. Research on brain neurotransmitters suggests that GFR can augment physiological functions such as learning and memory, while also inhibiting central nervous system excitation to a certain degree by maintaining the equilibrium of central neurotransmitters in aged individuals. Twenty-four abnormal metabolites in serum and seventeen abnormal metabolites in brain could be used as potential biomarkers and were involved in multiple metabolic pathways. Among them, in the brain metabolic pathways, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, histidine metabolism, and tyrosine metabolism were closely related to central neurotransmitters. Butanoate metabolism improves energy supply for life activities in the aging body. Cysteine and methionine metabolism contributes to the production of glutathione and taurine and played an antioxidant role. In serum, the regulation of glycerophospholipid metabolism pathway and proline metabolism demonstrated the antioxidant capacity of GFR decoction. Conclution: In summary, GFR plays a role in delaying aging by regulating central neurotransmitters, cardiovascular function, oxidative stress, energy metabolism, and other aspects of the aging body, which lays a foundation for the application of GFR.

6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1β (IL-1β), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

Short- and Long-Term Neurobehavioral Effects of Developmental Exposure to Valproic Acid in Zebrafish.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research.

Sexual dimorphism in neurobehavioural phenotype and gut microbial composition upon long-term exposure to structural analogues of bisphenol-A

Bisphenol S (BPS) and Bisphenol F (BPF), the analogues of the legacy endocrine disrupting chemical, Bisphenol A (BPA) are ubiquitous in the environment and present in various consumer goods, and potentially neurotoxic. Here, we studied sex-specific responses of bisphenols on behavioural phenotypes, including their association with pro-inflammatory biomarkers and altered neurotransmitters levels, and the key gut microbial abundances. Neurobehavioural changes, using standard test battery, biochemical and molecular estimations for inflammatory cytokines, neurotransmitters, and oxido-nitrosative stress markers, gene expression analysis using qRT-PCR, H&E based histological investigations, gut permeability assays and Oxford Nanopore-based 16S-rRNA metagenomics sequencing for the gut microbial abundance estimations were performed. Bisphenol(s) exposure induces anxiety and depression-like behaviours, particularly in the male mice, with heightened pro-inflammatory cytokines levels and systemic endotoxemia, altered monoamine neurotransmitters levels/turnovers and hippocampal neuronal degeneration and inflammatory responses in the brain. They also increased gut permeability and altered microbial diversity, particularly in males. Present study provides evidence for sex-specific discrepancies in neurobehavioural phenotypes and gut microbiota, which necessitate a nuanced understanding of sex-dependent responses to bisphenols. The study contributes to ongoing discussions on the multifaceted implications of bisphenols exposure and underscores the need for tailored regulatory measures to mitigate potential health risks associated with them.

Hematological and neurological impact studies on the exposure to naturally occurring radioactive materials

Naturally Occurring Radioactive Materials (NORM) contribute to everyone's natural background radiation dose. The technologically advanced activities of the gas and oil sectors produce considerable amounts of radioactive materials as industrial by-products or waste products. The goal of the current study is to estimate the danger of long-term liability to Technologically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) on blood indices, neurotransmitters, oxidative stress markers, and β-amyloid in the cerebral cortex of rats' brains. Twenty adult male albino rats were divided into two equal groups (n = 10): control and irradiated. Irradiated rats were exposed to a total dose of 0.016 Gy of TE-NORM as a whole-body chronic exposure over a period of two months. It should be ''The results showed no significant changes in RBC count, Hb concentration, hematocrit percentage (HCT%), and Mean Corpuscular Hemoglobin Concentration (MCHC). However, there was a significant increase in the Mean Corpuscular Volume of RBCs (MCV) and a significant decrease in cell distribution width (RDW%) compared to the control. Alteration in neurotransmitters is noticeable by a significant increase in glutamic acid and significant decreases in serotonin and dopamine. Increased lipid peroxidation, decreased glutathione content, superoxide dismutase, catalase, and glutathione peroxidase activities indicating oxidative stress were accompanied by increased β-amyloid in the cerebral cortex of rats' brains. The findings of the present study showed that chronic radiation liability has some harmful effects, that may predict the risks of future health problems in occupational radiation exposure in the oil industries. Therefore, the control of exposure and application of sample dosimetry is recommended for health and safety.

Effectiveness of Psychobiotic Bifidobacterium breve BB05 in Managing Psychosomatic Diarrhea in College Students by Regulating Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled Trial.

Diarrhea of college students (DCS) is a prevalent issue among college students, affecting their daily lives and academic performance. This study aims to explore the potential effect of Bifidobacterium breve BB05 supplements on the DCS. Initially, fifty healthy and fifty diarrheal students were recruited in the observational experiment and allocated into control and diarrhea groups, respectively. Subsequently, one hundred diarrheal students were newly recruited in the intervention experiment and randomly allocated into placebo and probiotic groups, both treated for 2 weeks. Questionnaires (BSS, HAMA-14, and HDRS-17) were performed to assess the students' diarrheal states and mental health at baseline and post-treatment. Fecal samples underwent 16S rRNA sequencing and Enzyme-Linked Immunosorbent Assay to evaluate gut microbiota and fecal metabolite alternations. Results indicated that B. breve BB05 supplementation significantly enriched (p < 0.05) the reduced gut microbial diversity caused by diarrhea. Diarrhea resulted in notable alterations in gut microbiota composition, as exhibited by elevated Collinsella and Streptococcus, alongside substantially decreased Bifidobacterium, Bacteroides, and Prevotella, while B. breve BB05 supplementation partially restored the compromised gut microbiota at both the phylum and genus levels, particularly by increasing Bifidobacterium and Roseburia (p < 0.05). Importantly, questionnaire results suggested that B. breve BB05 administration achieved superior efficacy in relieving diarrhea symptoms and the associated anxiety and depression in college students. An increased fecal concentration of 5-hydroxytryptamine (5-HT) was also observed in the probiotic group, while Acetylcholine (ACH), Epinephrine (EPI), and Noradrenaline/Norepinephrine (NANE) reduced, revealing the potential of B. breve BB05 in alleviating anxiety and depression via modulating the microbiota-gut-brain axis. Furthermore, correlation analysis suggested that the altered microbiota and fecal neurotransmitters were closely associated with the mental symptoms. These results endorse B. breve BB05 intervention as a promising and innovative approach to alleviate both diarrhea and mental health conditions among college students.

Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Antidepressant Effect of Vincamine, Melatonin and their Combination in Experimental Rat Models of Depression

Background: Depression, a form of mood illness, is characterized by a lack of or diminished social life, melancholy, and symptoms linked to an uplifted or depressed mood. Vincamine and Melatonin combination may prove beneficial for treating depression because vincamine and melatonin have already been reported in the treatment of dementia. Dementia is a CNS disorder which is connected to the level of neurotransmitters at the synaptic cleft, which is similar to depression that is why it might be effective in the treatment of depression. Aim: The aim of this research is to conduct an experimental study on the antidepressant activity of Vincamine alone and along with Melatonin and comparison with standard antidepressant drugs. Method: In this study, all animals are trained for the experiment, and then animals are divided into groups according to the treatment protocol. Animals were placed for the rest for 1 week. Vincamine and melatonin were administered to the treated groups on days 8 and 21 for the behavioral analysis using different kinds of models like elevated plus maze, forced swim test, open field test and sucrose preference test. Animals were sacrificed at day 22 for the estimation of biochemical (SOD) and neurotransmitters (Serotonin, Norepinephrine and Dopamine). Results: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10 mg/kg), Melatonin (10 mg/kg), Vincamine + Melatonin (10 mg/kg + 10 mg/kg) and std (10 mg/kg) treatment showed significant result which are followed as for all groups (a) p &lt; 0.0001 vs NC; (b) p &lt; 0.0001 vs disease control; (c) p &lt; 0.05 vs Std (10 mg/kg); (d) p &lt; 0.001V vs M (10 mg/kg); (e) p &lt; 0.0090 vs V+M (10 mg/kg+10 mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p &lt; 0.0001) in the evaluation of the SOD antioxidant defence system. Also, it significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. result: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10mg/kg), Melatonin (10mg/kg), Vincamine + Melatonin (10mg/kg + 10mg/kg) and std (10mg/kg) treatment showed significant result which are followed as for all groups (a) p &amp;amp;lt; 0.0001 vs NC; (b) p &lt; 0.0001 vs disease control; (c) p &lt; 0.05 vs Std (10 mg/kg); (d) p &lt; 0.001V vs M (10 mg/kg); (e) p &lt; 0.0090 vs V+M (10mg/kg+10mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p&lt;0.0001) in the evaluation of the SOD antioxidant defence system. Also, significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. Conclusion: It has been concluded that vincamine alone and along with melatonin is effective for the treatment of depression on the basis of behavioural and biochemical parameters. That’s why it might be useful for the future prospect.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Alterations of neurotransmitters and metabolite levels in a rat model of orofacial dyskinesia

Alterations of neurotransmitters and metabolite levels in a rat model of orofacial dyskinesia

Emerging role of rolipram in orofacial dyskinesia in a haloperidol-induced rat model via downregulation of oxidative stress and alteration in neurotransmitters

Emerging role of rolipram in orofacial dyskinesia in a haloperidol-induced rat model via downregulation of oxidative stress and alteration in neurotransmitters

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective.

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

Enrofloxacin exposure undermines gut health and disrupts neurotransmitters along the microbiota-gut-brain axis in zebrafish

The environmental prevalence of antibiotic residues poses a potential threat to gut health and may thereby disrupt brain function through the microbiota-gut-brain axis. However, little is currently known about the impacts of antibiotics on gut health and neurotransmitters along the microbiota-gut-brain axis in fish species. Taking enrofloxacin (ENR) as a representative, the impacts of antibiotic exposure on the gut structural integrity, intestinal microenvironment, and neurotransmitters along the microbiota-gut-brain axis were evaluated in zebrafish in this study. Data obtained demonstrated that exposure of zebrafish to 28-day environmentally realistic levels of ENR (6 and 60 μg/L) generally resulted in marked elevation of two intestinal integrity biomarkers (diamine oxidase (DAO) and malondialdehyde (MDA), upregulation of genes that encode inter-epithelial tight junction proteins, and histological alterations in gut as well as increase of lipopolysaccharide (LPS) in plasma, indicating an evident impairment of the structural integrity of gut. Moreover, in addition to significantly altered neurotransmitters, markedly higher levels of LPS while less amount of two short-chain fatty acids (SCFAs), namely acetic acid and valeric acid, were detected in the gut of ENR-exposed zebrafish, suggesting a disruption of gut microenvironment upon ENR exposure. Along with corresponding changes detected in gut, significant disruption of neurotransmitters in brain indicated by marked alterations in the contents of neurotransmitters, the activity of acetylcholin esterase (AChE), and the expression of neurotransmitter-related genes were also observed. These findings suggest exposure to environmental antibiotic residues may impair gut health and disrupt neurotransmitters along the microbiota-gut-brain axis in zebrafish. Considering the prevalence of antibiotic residues in environments and the high homology of zebrafish to other vertebrates including human, the risk of antibiotic exposure to the health of wild animals as well as human deserves more attention.