Changes In Neurotransmission Research Articles

Robust congregation influences of AB-PINACA and MDMB-4en-PINACA inhalation on neurobehavioral and cardiac disorders in mice

BackgroundA novel category of unusual cannabinoid substances was created to serve as marijuana alternatives due to its widespread availability, low price, pleasurable effects, and difficulty to be detected in regular urine testing for drugs, although more potential for abuse, toxicity, and behavioral alterations can result. It is more hazardous to multiple organ systems and has higher CB1 and CB2 receptor affinities than natural cannabinoids. So, the abuse potential, toxicity, and cardiac and nervous systems health hazards of two popular street herbs (AB-PINACA and MDMB-4en-PINACA) have been evaluated in mice.MethodsThirty male mice were separated into three equally sized groups indiscriminately: the control group: received no treatments, the AB-PINACA-treated group, and the MDMB-4en-PINACA-treated group. Treated groups were exposed to the two herbs for two consecutive days via inhalation to simulate natural human exposure. Cannabinoid tetrad tests and anxiety-like behavior were performed. Serum samples were obtained for cardiac enzymes measurement. Heart and brain tissue samples were harvested for the determination of oxidative stress markers, brain neurotransmitters, and histopathological findings.ResultsNociception and hypothermia were significantly influenced by both treatments. The locomotor activity decreased significantly with AB-PINACA inhalation, while the cataleptic effect increased significantly with MDMB-4en-PINACA inhalation. In addition, both treatments induced anxiety-like behavior. Both treatments induced alterations in brain neurotransmitter levels (glutamate, dopamine, and serotonin) and cardiac enzyme levels (CK-MB, troponin I). Histological changes showed neurodegenerative, necrotic, and infracted heart myocytes and degenerated muscle fibers, particularly with MDMB-4en-PINACA inhalation.ConclusionsAcute inhalation of street herbs containing AB-PINACA and MDMB-4en-PINACA induced neurobehavioral and cardiac disturbances, which were evident by changes in behavior, brain neurotransmitters, and heart enzymes, in addition to the degenerative histopathological changes in the brain and heart.

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 μM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.

Behavioral and neurotransmitter changes on antiepileptic drugs treatment in the zebrafish pentylenetetrazol-induced seizure model

Epilepsy, a recurrent neurological disorder involving abnormal neurotransmitter kinetics in the brain, has emerged as a global health concern. The mechanism of epileptic seizures is thought to involve a relative imbalance between excitatory and inhibitory neurotransmitters. Despite the recent advances in clinical and basic research on the pathogenesis of epilepsy, the complex relationship between the neurotransmitter changes and behavior with and without antiepileptic drugs (AEDs) during seizures remains unclear. To investigate the effects of AEDs such as levetiracetam (LEV), carbamazepine (CBZ), and fenfluramine (FFR) on key neurotransmitters in the pentylenetetrazol (PTZ)-induced seizures in adult zebrafish, we examined the changes in glutamic acid, gamma-aminobutyric acid (GABA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), choline, acetylcholine, norepinephrine, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and adenosine. In this study, we observed that 5-HT and DA levels in the brain increased immediately after PTZ-induced seizures. Behavioral tests clearly showed that all of these AEDs suppressed the PTZ-induced seizures. Upon treatment of PTZ-induced seizures with these AEDs, CBZ decreased the glutamic acid and FFR increased the GABA levels; however, no neurotransmitter changes were observed in the brain after LEV administration.Thus, we demonstrated a series of neurotransmitter changes linked to behavioral changes during PTZ-induced epileptic seizures when LEV, CBZ, or FFR were administered. These findings will lead to a more detailed understanding of the pathogenesis of epilepsy associated with behavioral and neurotransmitter changes under AED treatment.

Premenstrual syndrome and premenstrual dysphoric disorder-Overview on pathophysiology, diagnostics and treatment

Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as adifferential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From apathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by acomplex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.

Early Life Stress and Major Depressive Disorder-An Update on Molecular Mechanisms and Synaptic Impairments.

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms.

Dysfunction of neurotransmitter metabolism is associated with the severity of depression in first-diagnosed, drug-naïve depressed patients

Background & aimsBiochemical changes of neurotransmitters underlying major depressive disorder (MDD) are unknown. This study preliminarily explored the association between neurotransmitters with MDD and the possibility of objective laboratory prediction of neurotransmitter involvement in MDD. MethodsA total of 87 first-diagnosed, drug-naïve patients with depression and 50 healthy controls (HCs) were included in the cross-sectional study. The levels and turnovers of neurotransmitters (glutamine (GLN), glutamic acid (GLU), γ-2Aminobutiric acid (GABA), kainate (KA), vanillylmandelic acid (VMA), 3-methoxy 4-hydroxyphenyl ethylene glycol (MHPG), noradrenaline (NE), homovanillic acid (HVA), dihydroxy-phenyl acetic acid (DOPAC), dopamine (DA), tryptophane (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) were determined and the confounding factors were adjusted. Then a correlation and a predictive analysis towards neurotransmitters for MDD were performed. ResultsAfter adjusting confounding factors, GLU (OR = 1.159), (GLU+ GABA)/GLN (OR = 1.217), DOPAC (OR = 1.106), DOPAC/DA (OR = 1.089) and (DOPAC+ HVA)/DA (OR = 1.026) enacted as risk factors of MDD, while KYN (OR = 0.992) was a protective factor. GABAergic and TRPergic pathways were associated with severity of depressive and anxiety symptoms in patients with depression. The predictive model for MDD (AUC = 0.775, 95%CI 0.683–0.860) consisted of KYN (OR = 0.990) and (GLU + GABA)/GLN (OR = 4.101). ConclusionsFirst-diagnosed, drug-naïve depression patients showed abnormal neurotransmitter composition. GLU, (GLU + GABA)/GLN, DOPAC, DOPAC/DA and (DOPAC + HVA)/DA were risk factors of MDD, while KYN was a protective factor. GABAergic and TRPergic pathways were correlated with MDD clinical characteristics. KYN and (GLU + GABA)/GLN may have a predictive value for MDD.

Unveiling MRI markers for Parkinson’s Disease: GABAergic dysfunction and cortical changes

ObjectiveThe study aimed to investigate changes in basal levels of the inhibitory γ-aminobutyric acid (GABA) neurotransmitter in the sensorimotor cortex (SMC) and cortical gyrification in patients with Parkinson’s disease (PD), which could further identify potential imaging biomarkers for PD, particularly in patients with early-onset Parkinson’s disease (EOPD). MethodFifty patients with PD (EOPD: 10, late-onset Parkinson’s disease [LOPD]: 40) and fifty-two age- and gender-matched healthy controls (HC) underwent GABA-edited 1H MRS of the SMC and high-resolution 3D T1-weighted brain imaging. GABA levels and local gyrification index (LGI) were calculated to assess GABAergic and cortical gyrification deficits in PD. ResultThe Pearson correlation coefficients revealed significant negative associations between eight indicators, including GABA/Cr level and local gyrification index (LGI) of specific cortical regions (precentral, postcentral, entorhinal, superiortemporal, posteriorcingulate, cuneus, and transversetemporal cortex), and the likelihood of Parkinson’s disease (r < -0.4, p < 0.001). Additionally, GABA levels were significantly lower in the SMC region of both EOPD and LOPD patients compared to healthy controls (mean ± SD [u.i.]: EOPD=0.081 ± 0.022 vs. Young-HC=0.112 ± 0.021, p = 0.003; LOPD=0.054 ± 0.024 vs. Old-HC=0.099 ± 0.021, p < 0.001). The logistic regression model was established by using multivariate analysis, identifying two statistically significant indicators: GABA/Cr and LGI of the transversetemporal. The combined model exhibited the highest AUC values in both younger and older populations. ConclusionGABAergic dysfunction may play an important role in the pathogenesis of PD patients. Changes in neurotransmitter and morphological may serve as potential markers for the preclinical diagnosis and progression of PD, including EOPD.

Neurotransmitter changes and behavioral manifestations in mouse models of Parkinson's disease

Neurotransmitter changes and behavioral manifestations in mouse models of Parkinson's disease

Phytochemical screening, antioxidant and anti-Parkinson activities of Berula erecta: A novel medicinal plant.

Berula erecta L. is traditionally used for the treatment of various human ailments. The present project was arranged to study the antioxidant and anti-Parkinson efficacy of B. erecta extracts against rotenone-induced Parkinson diseases in rats. Fine powder of the plant was extracted with methanol and then fractionated through various solvents with increasing order of polarity. Phytochemical screenings were done using standard protocols and High-performance liquid chromatography (HPLC) while in-vitro antioxidant activities of plant fractions were evaluated using different free radicals. In-vivo anti-Parkinson and oxidative dysfunction experiments were conducted in rats. Results revealed that various fractions possessed flavonoids, alkaloids, terpenoids saponins, tannin, anthraquinon, and phlobatanine, while terpeniods and alkaloids were absent in aqueous fraction. Chromatographic analysis of methanol fraction showed the presence of various bioactive compounds viz., vitexin, orientin, rutin, catechin and myricetin. In-vitro antioxidant activities of various fractions of Berula erecta (B.erecta) showed that methanol fraction has remarkable scavenging efficacy of 2,2-Diphenyl-1-picrylhydrazyl (DPPH), beta carotene, and superoxide free radicals followed by chloroform fraction. Free radicals produced by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Hydrogen peroxide (H2O2), and hydroxyl free radicals were considerably scavenged by methanol fraction followed by ethyl acetate fractions. In-vivo study of animal model showed that methanol fraction has significant recovery effects at behavioural, physiological and biochemical level against rotenone induced Parkinson disease. B.erecta has significantly improved rotenone-induced motor and nonmotor deficits (depression and cognitive impairments), increased antioxidant enzyme activity, and reduced neurotransmitter changes. It has been concluded from the present data that B.erecta enhances neurotransmitter levels by alleviating oxidative stress and antioxidant enzyme activity, hence improving motor activity, cognitive functioning, and decreasing depressed behavior. These data suggest that B. erecta may be a promising medicinal agent for reducing the risk and progression of Parkinson's disease.

Protective effects of Embelin in Benzo[α]pyrene induced cognitive and memory impairment in experimental model of mice

Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.

Frontotemporal lobar degeneration changes neuronal beta-frequency dynamics during the mismatch negativity response

The consequences of frontotemporal lobar degeneration include changes in prefrontal cortical neurophysiology, with abnormalities of neural dynamics reported in the beta frequency range (14–30 Hz) that correlate with functional severity. We examined beta dynamics in two clinical syndromes associated with frontotemporal lobar degeneration: the behavioral variant of frontotemporal dementia (bvFTD) and progressive supranuclear palsy (PSP). Whilst these two syndromes are partially convergent in cognitive effects, they differ in disease mechanisms such as molecular pathologies and prefrontal atrophy. Whether bvFTD and PSP also differ in neurophysiology remains to be fully investigated. We compared magnetoencephalography from 20 controls, 23 people with bvFTD and 21 people with PSP (Richardson’s syndrome) during an auditory roving oddball paradigm. We measured changes in low and high total beta power responses (14–22 and 22–30 Hz respectively) over frontotemporal cortex in the period of the mismatch negativity response (100–250 ms post-stimulus). In controls, we found increased 14–22 Hz beta power following unexpected sensory events (i.e. increased deviant versus standard response), from right prefrontal cortex. Relative to controls, PSP reversed the mismatch response in this time–frequency window, reflecting reduced responses to the deviant stimuli (relative to standard stimuli). Abnormal beta at baseline in PSP could account for the reduced task-modulation of beta. Across bvFTD and PSP groups, the beta response to deviant stimuli (relative to standard stimuli) correlated with clinical severity, but not with atrophy of the prefrontal source region. These findings confirm the proposed importance of higher-order cortical regions, and their beta-power generators, in sensory change detection and context-updating during oddball paradigms. The physiological effects are proposed to result from changes in synaptic density, cortical neurotransmitters and subcortical connections, rather than merely atrophy. Beta-power changes may assist clinical stratification and provide intermediate outcomes for experimental medicine studies of novel therapeutic strategies.

Mechanism of Traditional Chinese Medicine in Treating Migraine: A Comprehensive Review.

Migraine is a common neurological illness that causes a great burden on individuals and society. Many migraine patients seek relief through complementary and alternative therapies, with Traditional Chinese medicine (TCM) often being their preferred choice. Acupuncture, Chinese herbal medicine, and massage are important components of TCM, and are commonly used in clinical treatment of migraine. This review aims to consolidate the current knowledge regarding the mechanisms of the three TCM interventions for migraine: acupuncture, herbs, and massage, and how they relieve pain. However, the mechanisms underlying the effectiveness of TCM therapies in treating migraine remain unclear. Therefore, we reviewed the research progress on acupuncture, herbal medicine, and massage as TCM approaches for the treatment of migraine. We conducted a comprehensive search of CNKI, PubMed, Web of Science, and Cochrane databases using keywords such as migraine, acupuncture, needle, herbs, herbal, prescription, decoction, massage, Tuina, and TCM, covering the period from 2000 to 2023. The literature included in the review was selected based on specified exclusion criteria. We discussed the mechanism of TCM therapies on migraine from the perspective of modern medicine, focusing on changes in inflammatory factors, neurotransmitters, and other relevant biomarkers. TCM can relieve migraine by decreasing neuropeptide levels, inhibiting inflammation, modulating neuronal sensitization, changing brain function and structure, changing blood brain barrier permeability, regulating hormone levels, and relieving muscle tension. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of migraine.

Morus alba; A Ray of Hope for Psychiatric Illnesses

Purpose: Over the years, plants have been used in treatment of various health ailments. Morus alba also known as White Mulberry is a deciduous tree which belongs to family Moraceae. Mulberry is rich in antioxidants such as hydrophobic flavonoids, polyphenols, carotenoids, vitamin A, C and E.&#x0D; Materials and Methods: This study analyses the central nervous system activities including memory enhancement, learning abilities, changes in behavior, cognition, anxiety and depression. These effects will be studied on experimental mice, which will be distributed in control and test groups. Aqueous fruit extract prepared by Maceration extraction will be given to test group in three different doses per oral over a time period of 30 days, whereas control will be given water for injection for same duration.&#x0D; Findings: Afterwards, changes in aforementioned effects will be observed to determine the pharmacological effects of taken fruit. The obtained results suggest an antidepressant like effect of mulberry in the initial two weeks of dosing. Afterwards it shows anxiolytic effect at higher doses.&#x0D; Implications to Theory, Practice and Policy: All these tests can be repeated weekly while dosing the animals daily for 90 days for chronic toxicity analysis. Furthermore, we can add a brain biopsy/histopathology to evaluate the changes in chemical neurotransmitters.

Co-exposure to sodium hypochlorite and cadmium induced locomotor behavior disorder by influencing neurotransmitter secretion and cardiac function in larval zebrafish

Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 μg/L), 1/100 Cd group (48 μg/L), 1/30 Cd group (160 μg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.

The Role of Molecular Aspects in the Occurrence of Febrile Seizures

Febrile seizures are the result of complex interactions between multiple molecular components in the child's central nervous system, including changes in neurotransmitters, neuronal activity, and the brain's inflammatory response. When a child has a fever, there is an increase in body temperature, which triggers a series of molecular changes in the brain, affecting electrical signaling pathways and triggering characteristic seizures. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding studies of molecular aspects of febrile seizures. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations. An increase in body temperature (fever) is the main trigger for febrile seizures. Fever can result in changes in brain chemistry, including changes in neurotransmitters and inflammatory responses, which can affect the molecular pathways that trigger seizures. Glutamate is the main neurotransmitter that plays a role in triggering seizures. Increased glutamate release during fever can trigger excessive activity in neurons. On the other hand, GABA, a neurotransmitter that plays a role in dampening neuronal activity, may also be involved, and an imbalance between glutamate and GABA may occur during seizures. Genetic factors play a role in susceptibility to febrile seizures. Several genes, such as SCN1A and GABRG2, have been identified as potentially increasing the risk of febrile seizures, especially those of a complex nature. Febrile seizures usually do not cause permanent changes in brain structure. However, in some very rare cases, such as EASIFE, temporary changes in brain structure may occur.

The Effects of Unilateral Labyrinthectomy on Monoamine Neurotransmitters in the Medial Vestibular Nucleus of Rats.

This study aimed to investigate the effects of unilateral labyrinthectomy (UL) on monoamine neurotransmitters in the medial vestibular nucleus (MVN) of rats. Adult Sprague-Dawley rats were utilized for the vestibular impaired animal model through UL. The success of the model establishment and the recovery process were evaluated using vestibular behavioral tests, including spontaneous nystagmus, postural asymmetry, and balance beam test. Additionally, the expression levels of c-Fos protein in the MVN were assessed by immunofluorescence. Furthermore, changes in the expression levels of monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and histamine in the MVN, were analyzed using high-performance liquid chromatography (HPLC) at different time points after UL (4 h, 8 h, 1 day, 2 days, 4 days, and 7 days). Compared to the sham control group, the UL group exhibited the most pronounced vestibular impairment symptoms at 4 h post-UL, which significantly decreased at 4 days and almost fully recovered by 7 days. Immunofluorescence results showed a notable upregulation of c-Fos expression in the MVN subsequent to the UL-4 h, serving as a reliable indicator of heightened neuronal activity. In comparison with the sham group, HPLC analysis showed that the levels of 5-HT and NE in the ipsilesional MVN of the UL group were significantly elevated within 4 days after UL, and peaked on 1 day and 2 days, respectively. DA showed an increasing trend at different time points up to 7 days post-UL, while histamine levels significantly increased only at 1 day post-UL. UL-induced dynamic changes in monoamine neurotransmitters during the early compensation period in the rat MVN may be associated with the regulation of the central vestibular compensation mechanism by the MVN.

Probiotic Lactobacillus rhamnosus alleviates the neurotoxicity of microcystin-LR in zebrafish (Danio rerio) through the gut-brain axis

Microcystin-LR (MCLR) is one of the most toxic cyanobacterial toxins and is harmful to the central nervous system of fish. Probiotic additives can improve neuroendocrine function in fish. Although both MCLR and probiotics aim at the nervous system, whether they interact with each other and the mechanisms remain unexplored. In the present study, 4-month-old zebrafish were exposed to 0, 2.2, and 22 μg/L of MCLR for 28 days with or without the probiotic L. rhamnosus. We found that MCLR exposure could inhibit the swimming speed of zebrafish, while the presence of L. rhamnosus mitigated this abnormality. To elucidate the mechanism of how L. rhamnosus alleviates MCLR-induced neurotoxicity, we examined the bioaccumulation of MCLR, changes in neurotransmitters, immune biochemical indicators, and hormone content of the hypothalamic-pituitary-interrenal (HPI) axis in zebrafish along the gut-brain axis. Our results showed L. rhamnosus could reverse the abnormal swimming behavior and eventually alleviate neurotoxicity in zebrafish by modulating intestinal and brain neural signaling, neuroinflammation, and HPI axis responses. This study provides implications for the application of probiotics in the aquaculture industry.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank. Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.

Retinal Neurotransmitter Alteration in Response to Dopamine D2 Receptor Antagonist from Myopic Guinea Pigs.

This study aimed to investigate the changes in retinal neurotransmitters and the role of the dopamine D2 receptor (D2R) pathway in regulating the myopic refractive state. Tricolor guinea pigs were randomly divided into two groups: the normal control group (NC) and the form-deprivation myopia group (FDM). Animals in the FDM group had their right eye covered with a balloon for 4 weeks. These two groups were further divided into two subgroups based on intravitreal injection with D2R antagonist sulpiride once a week for 3 weeks (NC, NC-Sul, FDM, and FDM-Sul groups). Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to quantitatively detect the changes in 17 retinal neurotransmitters. Compared to the NC group, the concentrations of dopamine (DA) and γ-aminobutyric acid (GABA) decreased, while those of glutamate (Glu), 3-methoxytyramine (3-MT), and glycine increased, accompanied by an increase in myopic refraction and axial length (AL) in the FDM group. In the FDM-Sul group, glycine and DA levels were upregulated, whereas 3-MT and Glu levels were downregulated, accompanied by a decrease in myopic refraction and AL. The ratio of Glu to GABA (RGG) represents the balance between excitatory and inhibitory neurotransmitters. Notably, RGG changes occurred with corresponding AL changes, which increased in the FDM group and decreased in the FDM-Sul group. Decreased retinal DA concentration, with an increase in Glu, may be involved in the myopia progression. D2R antagonists might effectively slow myopia progression by increasing retinal DA, regulating Glu concentration to match GABA, and maintaining the balance between excitatory and inhibitory neurotransmitters.

Unraveling neurotransmitter changes in de novo GBA-related and idiopathic Parkinson's disease

BackgroundPresently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD — particularly in the newly diagnosed drug-naïve phase — may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations. MethodsWe recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age- and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems. ResultsGBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function and language in cognitive domains were also associated with the strength of GMV colocalization of serotonergic, dopaminergic, and acetylcholinergic circuits. ConclusionsRegional GM atrophy related to specific neurotransmitter deficits in de novo GBA-PD and iPD patients could provide new insights into pathophysiological processes, facilitating potential therapeutic targets to support PD management.