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Currently, neurological disorders are the primary global cause of illness and disability. Transcranial ultrasound stimulation in the deep brain has limited spatial resolution. However, ultrasound can enhance energy propagation resolution affected by tissue and bone dispersion. Among the non-invasive imaging methods in this category are biochemical assays that measure GABA levels and the highly expensive Magnetic Resonance Spectroscopy (MRS). Gamma-Aminobutyric Acid (GABA), a major neurotransmitter in the brain, contributes to 40% of inhibitory synapses in adult vertebrates. Biosensors such as piezoelectric sensors and the MPU6050 can accurately determine GABA levels in the nervous system. This system uses a Micro Processing Unit (MPU) and a piezoelectric pressure sensor to detect changes in GABA levels, which are essential for maintaining neurological health and balance. The system provides real-time data on GABA levels, and this high-accuracy information is displayed on an LCD panel. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a complex, multifactorial and most prevalent progressive neurodegenerative ailment. Its multifactorial and complex nature causes the lack of disease modifying drugs. Hence, multi-target drug design strategies have been adopted to halt the progression of AD. In current research, we applied multitarget strategy to tackle multifactorial nature of AD. Rational design and synthesis of framework of hybrids containing Pyrimidine/pyrrolidine-sertraline scaffolds were carried out. The synthesized compounds were further evaluated for their in-vitro enzyme inhibition potential against cholinesterases, monoamine oxidases and β-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Compound 19 emerged as an optimal multipotent hybrid with IC50 values of 0.07 µM, 0.09 µM, 0.63 µM, 0.21 µM and 0.73 µM against AChE, BChE, MAO-A, MAO-B and BACE-1 respectively. After in-vivo cytotoxicity and in-vitro PAMPA blood brain barrier permeation assays, a number of widely used behavioral assessment tests were also performed for the evaluation of memory and learning.Determination of biochemical parameters showed low levels of acetylcholinesterase by the treatment with synthesized compounds. Furthermore, levels of neurotransmitters such as serotonin, dopamine and noradrenaline were also analyzed. Increased neurotransmitter levels showed the improved short and long-term memory as well as enhanced learning behavior. Docking studies on the target enzymes showed correlation with the experimental in-vitro enzyme inhibition results.

Thimerosal (THI) is an organic mercury compound that is widely used in drugs, vaccines and antibacterial products. Its extensive production and use have resulted in significant environmental contamination, posing a considerable threat to aquatic life. However, the knowledge of the toxicity of THI to aquatic organisms is still insufficient. In this study, we conducted a 5-day THI exposure experiment using zebrafish, from 0 to 5 days post fertilization (dpf). The possible adverse effects of THI on the early-life stages of zebrafish were explored by investigating variations in their physiological parameters, behavioral traits, and neurotransmitter levels. The results showed THI exhibited significant developmental toxicity to aquatic organisms. Exposure to THI significantly induced serious malformation (at 50 μg/L), accelerated hatching, and elevated heart rate (at 5 and 50 μg/L). The behavioral traits of zebrafish larvae had an increased first and then decreased relationship with increasing concentration of THI, which induced hyperactivity at 0.5 μg/L but opposite at 50 μg/L. Furthermore, exposure to 50 μg/L THI significantly raised levels of 5-HT, 5-HIAA, DA, DOPAC and ACH in zebrafish larvae. In addition, several significant correlations between behavioral traits and the neurotransmitter contents were detected, which seemed to reveal an important mechanism of the neurobehavioral toxicity of THI to fish., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper named”Adverse effects of thimerosal on the early life stages of zebrafish”., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peganum harmala L., a traditional Uyghur ethnic medicine widely used in China, is commonly used in the treatment of conditions such as hemiplegia, forgetfulness, cough, and asthma. Harmine and other β-carboline alkaloids, one of the main active ingredients in P. harmala , have exhibited various pharmacological activities, including anti-Alzheimer's, antidepressant, anti-inflammatory, and antioxidant effects. However, the effects and underlying mechanisms of harmine on improving ethanol-induced memory impairment remain unclear. This study aimed to investigate the effects of harmine on ameliorating ethanol-induced memory impairment, and to explore potential mechanisms. Ethanol (30%, i. g.) was used to induce memory impairment model. The effect of harmine on memory impairment was evaluated by Morris water maze (MWM). The histopathological analysis, immunofluorescence staining, RT-qPCR and UHPLC-MS/MS methods were performed to further investigate the underlying mechanisms. MWM experiments showed that harmine significantly improved ethanol-induced spatial learning memory deficit. Harmine exhibited anti-inflammatory effect by downregulating inflammatory factors such as IL-6, IL-1β and tumor necrosis factor-α (TNF-α) induced by ethanol. Harmine also upregulated brain-derived neurotrophic factor (BDNF) levels to exert neuroprotective effect. Moreover, harmine protected neuronal cells and increased the protein expression of myelin basic protein (MBP). The cellular results indicated that harmine protected SH-SY5Y cells from ethanol-induced cytotoxicity and upregulated the relative mRNA expression of synaptosome associated protein 25 (SNAP25), syntaxin 1 A (STX1A), vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (SYT1) and synaptophysin (SYP). Harmine improved ethanol-induced memory impairment by ameliorating inflammation, increasing BDNF levels, promoting synaptic vesicle fusion, protecting myelin sheath, and modulating neurotransmitter levels. These findings provided a scientific basis for development of therapeutic drugs for alcohol-induced memory impairments and other related disorders. [Display omitted] • Harmine is one of the active ingredients in P. harmala with anti-AD activity. • The MWM test confirmed that ethanol could induce memory impairment. • Harmine could ameliorate ethanol-induced memory impairment. • Harmine could improve inflammation, increase BDNF levels and protect neuronal cells. • Harmine could regulate neurotransmitter levels and promoted synaptic vesicle fusion. [ABSTRACT FROM AUTHOR]

Unpredictable chronic mild stress (UCMS) has been shown to cause memory loss via increased oxidative stress and deregulation of monoaminergic and cholinergic neurotransmissions. Although the benefits of methyl jasmonate (MJ), a well-known anti-stress plant hormone against chronic stress-induced psychopathologies, have been earlier reported, its effects on antioxidant defense molecules, monoaminergic transmitters, and nuclear factor erythroid 2-related factor 2 (Nrf2) immunopositive cells have not been extensively studied. The present study was designed to examine its effect on memory functions, antioxidant biomarkers, monoaminergic transmitters, and Nrf2 immunopositive cell expression in rats exposed to UCMS. Rats received an intraperitoneal injection of MJ (10, 25, and 50 mg/kg) 30 min before exposure to UCMS daily for 28 days. Memory function was assessed on day 29 using a modified elevated plus maze and novel object recognition tests. The antioxidant biomarkers, level of monoamines (serotonin, noradrenaline, and dopamine), and Nrf2 immunopositive cell expression were determined in the rat brain tissues. The activity of cholinesterase and monoamine oxidase enzymes was also determined. MJ attenuated memory deficits and elevated the brain levels of monoamines in UCMS rats. UCMS-induced increase of brain cholinesterase and monoamine oxidase activities was inhibited by MJ. Also, MJ attenuated UCMS-induced decrease in antioxidant enzymes (CAT, GPx, GST, and SOD) and thiol contents in the brains of rats. UCMS-induced increase in NO level and Nrf2 immunopositive cell expression in the rat's brain was attenuated by MJ. Taken together, these findings suggest that increasing antioxidant defense molecules and monoaminergic/cholinergic neurotransmitters and decreasing the Nrf2 immunopositive cell expressions may contribute to the memory-promoting effects of MJ in rats exposed to UCMS. [ABSTRACT FROM AUTHOR]

We have investigated the effects of 0.001 mg/kg 2-arachidonoylglycerol (2-AG) administered in combination with compounds present in the body alongside 2-AG like 2-palmitoylglycerol and 2-linoleylglycerol (also termed “entourage”), on cognitive function,food intake, and neurotransmitter levels in the hippocampus and hypothalamus of mice under diet restriction. Young female Sabra mice were treated with vehicle, 2-AG, 2-AG + entourage, 2-AG + entourage + 5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)- 4-methyl- N -(piperidin-1-yl)-1 H-pyrazole-3-carboxamide (SR141716A, a CB 1 antagonist) and SR141716A. The mice were fed for 2.5 h a day for 14 days. Cognitive function was evaluated by the eight arm maze test, and neurotransmitter (norepinephrine, dopamine, L-DOPA and serotonin) levels were measured in the hippocampus and hypothalamus by high-performance liquid chromatography-electrochemical detection. Food intake was increased by 2-AG and, to an even greater extent, by 2-AG + entourage. SR141716A reversed the effect of 2-AG + entourage. The administration of 2-AG + entourage improved cognitive function compared to the vehicle mice, and this improvement was blocked by SR141716A. 2-AG + entourage-treated mice showed an increase in norepinephrine (NE), dopamine and L-DOPA levels in the hippocampus. SR141716A normalized NE and L-DOPA levels. There were no significant changes in hypothalamic neurotransmitter levels. The use of very low doses of the endocannabinoid 2-AG + entourage can improve cognitive function by elevating norepinephrine and L-DOPA levels in the hippocampus, without cannabinomimetic side effects. These findings may have implications for cognitive enhancement in anorexia nervosa. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex, multifactorial and most prevalent progressive neurodegenerative ailment. Its multifactorial and complex nature causes the lack of disease modifying drugs. Hence, multi-target drug design strategies have been adopted to halt the progression of AD. In current research, we applied multitarget strategy to tackle multifactorial nature of AD. Rational design and synthesis of framework of hybrids containing Pyrimidine/pyrrolidine-sertraline scaffolds were carried out. The synthesized compounds were further evaluated for their in-vitro enzyme inhibition potential against cholinesterases, monoamine oxidases and β-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Compound 19 emerged as an optimal multipotent hybrid with IC 50 values of 0.07 µM, 0.09 µM, 0.63 µM, 0.21 µM and 0.73 µM against AChE, BChE, MAO-A, MAO-B and BACE-1 respectively. After in-vivo cytotoxicity and in-vitro PAMPA blood brain barrier permeation assays, a number of widely used behavioral assessment tests were also performed for the evaluation of memory and learning.Determination of biochemical parameters showed low levels of acetylcholinesterase by the treatment with synthesized compounds. Furthermore, levels of neurotransmitters such as serotonin, dopamine and noradrenaline were also analyzed. Increased neurotransmitter levels showed the improved short and long-term memory as well as enhanced learning behavior. Docking studies on the target enzymes showed correlation with the experimental in-vitro enzyme inhibition results. [Display omitted] • Rationally designed pyrimidine/pyrrolidine-sertraline based hybrids were synthesized. • Synthesized compounds were evaluated in-vitro against 5 molecular targets. • Excellent in-vivo behavioral assessment results of synthesized compounds were obtained. • Docking studies on all the 5 targets were performed to explore binding orientations. [ABSTRACT FROM AUTHOR]

Monoamine oxidases (MAO) influence the monoamine levels in brain by virtue of their role in neurotransmitter breakdown. MAO B is the predominant form in glial cells and in platelets. MAO B structure, function and kinetics are described as a background for the effect of alterations in its activity on behavior. The need to inhibit MAO B to combat decreased brain amines continues to drive the search for new drugs. Reversible and irreversible inhibitors are now designed using data-mining, computational screening, docking and molecular dynamics. Multi-target ligands designed to combat the elevated activity of MAO B in Alzheimer's and Parkinson's Diseases incorporate MAO inhibition (usually irreversible) as well as iron chelation, antioxidant or neuroprotective properties. The main focus of drug design is the catalytic activity of MAO, but the imidazoline I 2 site in the entrance cavity of MAO B is also a pharmacological target. Endogenous regulation of MAO B expression is discussed briefly in light of new studies measuring mRNA, protein, or activity in healthy and degenerative samples, including the effect of DNA methylation on the expression. Overall, this review focuses on examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B. [ABSTRACT FROM AUTHOR]

Abstract: In this study the long-term effects of morphine sulphate treatment (MST) on histopathological and biochemical changes in the cerebellum was assessed in albino rats. Normal saline (5ml) was given orally as placebo in the control group (n =25). Morphine groups received morphine orally at a dose level of 5mg/kg body weight day after day for 10, 20 and 30 days (n =25/group). Light microscopy revealed that the molecular layer showed vacuolation. The Purkinje cells lost their specific shaped appearance, decreased in size and numbers. The granular cells highly degenerated. Electron microscopy revealed fragmentation of the cisterns of the both types of endoplasmic reticulum, resulted in a progressive depletion of total protein contents as well as general carbohydrates in all treated groups as supported by histochemical observation. Obvious destruction of mitochondrial inner membrane and cristae mediate cell death. Also, abnormal nucleus with deformed perforated nuclear membrane and deformation of the plasma membrane with degeneration of the synapses could interpreted as a sign of necrosis. Biochemical analysis revealed that dopamine (DA) and norepinephrine (NE) were significantly decreased in four brain areas (cortex striatum, thalamus/hypothalamus, and cerebellum). In contrast, serotonin (5-HT) level was increased in these brain regions; with an exception of 5-HT on day 10 and neurotransmitter levels in the pons were unaffected. The quantitative analysis showed a significant decrease (P <0.05) in the diameter of Purkinje cells and in the thickness of both molecular and granular layers treated groups. Morphine sulphate induces may be a cell death or necrosis in the rat cerebellum and modulating neurotransmitter system. Our findings pointed out the risk of increased cerebellum damage due to long-term of morphine use. [Copyright &y& Elsevier]

The effects of repeated oral administration of the psychostimulant plant, Catha edulis and its active principle, cathinone on rats were studied using isolation induced aggression paradigm. The behavioral responses were videotaped and scored later by offline data analyses. Rats were decapitated at the end of the behavioral experiment and in the relevant brain regions, monoamines were assessed. The results demonstrate that isolation of male rats produces a baseline aggression. Treatments with the psychostimulant plant, Catha edulis or commercial S-(−)-cathinone enhanced significantly: The locomotor activities and the baseline aggression behaviors compared with vehicle treated rats. Neurochemical correlates revealed a significant depletion of serotonin (5-HT) and its corresponding metabolites (5-HIAA) in both the anterior and posterior striatum. There was also a reduction in the level of homovanillic acid (HVA) in the hippocampus. Additionally, elevation of dopamine level was observed in the nucleus accumbens, especially, in those rats treated with Catha edulis extract. Cathinone, on the other hand, increased the level of HVA in the posterior striatum and decreased HVA in the nucleus accumbens. In conclusion, the present data demonstrate that repeated administration of Catha edulis or S-(−)-cathinone enhances aggression in rats, presumably by decreasing the level of serotonin and its corresponding metabolites. Besides, the data obtained do not rule out the involvement of dopamine in aggression behavior. [ABSTRACT FROM AUTHOR]

We have investigated the effect of 0.001 mg/kg Δ8-tetrahydrocannabinol (THC) on food consumption, cognitive function, and neurotransmitters in mice. Sabra mice were treated with vehicle, THC, or THC+CB1 antagonist (SR141716A). The mice were fed for 2.5 h a day for 9 or 50 days. In the 9-day schedule, THC-treated mice showed a 16% increase in food intake compared with controls (P<.001). This effect was reversed by the antagonist (P<.01). In the long-term schedule a 22% increase in intake (P<.05) was recorded. During the course of the 9- and 50-day experimental protocol, all mice lost about 20% and 10% of their original weight, respectively, to reach approximately the same weights, which were not significantly different between the different treatment groups. In addition, THC caused an increase in activity (P<.05). Cognitive function showed a tendency to improve (P<.06) in the THC-treated mice, which was reversed by the antagonist for Days 4 and 5 of the maze (P<.01, and P<.05, respectively). Significant decreases in dopamine and serotonin (5-HT) levels were found both in the hypothalamus (P<.01) and the hippocampus (P<.01, P<.05), respectively, while norepinephrine (NE) levels showed tendency to increase in both the hypothalamus and hippocampus. Δ8-THC increased food intake significantly more (P<.05) than did Δ9-THC, while performance and activity were similar. Thus, Δ8-THC (0.001 mg/kg) caused increased food consumption and tendency to improve cognitive function, without cannabimimetic side effects. Hence, a low dose of THC might be a potential therapeutic agent in the treatment of weight disorders. [Copyright &y& Elsevier]