Neurochemical Studies Research Articles

Nano-pregabalin effectively mitigates Glut, CGRP and NE neurotransmitters abnormalities in the brain of gamma irradiated rats with reserpine-induced fibromyalgia model: Behavioral and neurochemical studies

AimsFibromyalgia (FM) is an idiopathic syndrome with painful burdensome symptoms. Radiotherapy is one of the main therapeutic modalities for treating various malignancies and there is a probable association between FM exacerbation and exposure to ionizing radiation. Based on that nanomedicines progressively being explored for their promising applications in medicine, the aim of the current study is to assess the possible therapeutic benefits of nanoform of pregabalin (N-PG) in managing FM symptoms during being exposed to ionizing radiation. Main methodsRats were allocated into four groups. First group served as control, the other three groups received gamma radiation (2 Gy/day) after 1 h of reserpine administration (1 ml/kg per day, s.c.) to induce FM for three successive days. On the next day, third and fourth groups received (30 mg/kg, p.o.) of PG and N-PG, respectively once daily for ten consecutive days. Tail flick test was performed and von Frey filaments were used to assess mechanical allodynia/hyperalgesia, and then rats were sacrificed to obtain brains. Key findingsN-PG effectively replenished reserpine effects and treated both allodynia and hyperalgesia, improved thermal allodynia, effectively recovered all neurotransmitters near to normal baseline, inhibited oxidative stress status via decreasing malondialdehyde (MDA), increasing glutathione (GSH) and superoxide dismutase (SOD), it had strong anti-inflammatory effect as verified by reducing both cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kB) in addition to inhibition of intrinsic apoptosis through caspase-3 (casp-3) decrease and B-cell lymphoma-2 (Bcl-2) increase. Histopathological and immunohistochemical results confirmed the biochemical findings. SignificanceN-PG could be a promising drug for treating FM especially when there is urgent need to expose patient to ionizing radiation.

Kratom-From natural remedy to addictive drug and back

Kratom/ketum is apsychoactive herbal preparation that has been used for along time as aremedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used. The current research on kratom and its ingredients is presented. An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed. Consumption is accompanied by several instrumentalizeable effects so that kratom is used as atherapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have acomplex pharmacology that involves partial µ‑opioid receptor agonism. Epidemiological, clinical and neurochemical studies have shown that kratom only has alimited addictive drug profile, which might suggest amedical use as aremedy or substitute in addiction treatment.

Comprehensive insights into Menkes disease: Genetics, pathophysiology, animal models, diagnosis, and therapeutic strategies

Menkes disease (MD) is an inherited disorder affecting primarily the males which is X-linked recessive in inheritance pattern due to mutation in ATP7A gene that codes for copper transporter protein. This results in neurological complications and connective tissue lesions that make affected males succumb to death. MD can be classified as the classical and Occipital Horn Syndrome (OHS) varieties, though the severity and early presentation of the classical MD is more pronounced. Diagnostic assays include determination of serum copper and ceruloplasmin concentrations; neurochemical studies are also performed. The standard treatment usually entails the use of copper supplements with copper – Histidine being one of the most effective. Therefore, it is necessary to investigate the molecular pathophysiology of ATP7A disorder to come up with different therapies. Animal models such as zebrafish, fruit flies etc. are beneficial to know about MD pathology to get treatment. In summary, the early and accurate diagnosis of MD, followed by immediate treatment, plays a critical role in successful management of the disorder.

The Association Between Chronic Tobacco Smoking and Brain Alterations in Schizophrenia: A Systematic Review of Magnetic Resonance Imaging Studies.

The high co-occurrence of tobacco smoking in patients with schizophrenia spectrum disorders (SSD) poses a serious health concern, linked to increased mortality and worse clinical outcomes. The mechanisms underlying this co-occurrence are not fully understood. Addressing the need for a comprehensive overview of the impact of tobacco use on SSD neurobiology, we conducted a systematic review of neuroimaging studies (including structural, functional, and neurochemical magnetic resonance imaging studies) that investigate the association between chronic tobacco smoking and brain alterations in patients with SSD. Eight structural and fourteen functional studies were included. Structural studies show widespread independent and additive reductions in gray matter in relation to smoking and SSD. The majority of functional studies suggest that smoking might be associated with improvements in connectivity deficits linked to SSD. However, the limited number of and high amount of cross-sectional studies, and high between-studies sample overlap prevent a conclusive determination of the nature and extent of the impact of smoking on brain functioning in patients with SSD. Overall, functional results imply a distinct neurobiological mechanism for tobacco addiction in patients with SSD, possibly attributed to differences at the nicotinic acetylcholine receptor level. Our findings highlight the need for more longitudinal and exposure-dependent studies to differentiate between inherent neurobiological differences and the (long-term) effects of smoking in SSD, and to unravel the complex interaction between smoking and schizophrenia at various disease stages. This could inform more effective strategies addressing smoking susceptibility in SSD, potentially improving clinical outcomes.

Altered Arginine/Agmatine Pathway and Polyamines in Adolescents Diagnosed with Major Depressive Disorder.

Major depressive disorder (MDD) is common in childhood, but its etiopathogenesis is still unclear. Published neurochemical studies mostly focus on monoaminergic system, however, the pathophysiology of MDD cannot be explained by monoamine hypothesis only, medications that have effect on monoamines cannot have effect needed in all patients. We aimed to investigate the poliamine pathway of L-arginine metabolism which is proceeding by way of agmatine in adolescents with MDD. Our study involved 45 patients with MDD (case group), and 44 healthy controls (control group) between the ages of 13-17. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version-DSM-5-Turkish, Beck Depression Inventory (BDI), Spielberger's State-Trait Anxiety Inventory were applied to all subjects. All subjects were evaluated in terms of the levels of serum agmatine, putrescine, spermidine, and spermine. The levels of agmatine and spermine were significantly higher and putrescine and spermidine were significantly lower in case group compared with healthy controls. There was significant negative correlation with the levels of putrescine and spermidine between BDI scores, and there was significant positive correlation between the levels of spermine and BDI scores. No correlation found between the levels of agmatine and BDI scores. These differences that the levels of agmatine and polyamines in the MDD group seem to be a field that worth researching. In the future, the evaluation of the arginine/polyamine metabolism in MDD with larger sample and longitudinal studies is going to capable to contribute to a better understanding of the disorder.

The neuropharmacological properties of α-pyrrolidinobutiothiophenone, a new synthetic cathinone, in rodents; role of the dopaminergic system.

α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT. We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D1 receptor or D2 receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents. α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D1 receptor antagonist SCH23390 or the D2 receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents. These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT.

Manganese and Vanadium Co-Exposure Induces Severe Neurotoxicity in the Olfactory System: Relevance to Metal-Induced Parkinsonism.

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V2O5) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl2, V2O5, and MnCl2-V2O5 co-exposure in an animal model. C57BL/6 mice were intranasally administered either de-ionized water (vehicle), MnCl2 (252 µg) alone, V2O5 (182 µg) alone, or a mixture of MnCl2 (252 µg) and V2O5 (182 µg) three times a week for up to one month. Following exposure, we performed behavioral, neurochemical, and histological studies. Our results revealed dramatic decreases in olfactory bulb (OB) weight and levels of tyrosine hydroxylase, dopamine, and 3,4-dihydroxyphenylacetic acid in the treatment groups compared to the control group, with the Mn/V co-treatment group producing the most significant changes. Interestingly, increased levels of α-synuclein expression were observed in the substantia nigra (SN) of treated animals. Additionally, treatment groups exhibited locomotor deficits and olfactory dysfunction, with the co-treatment group producing the most severe deficits. The treatment groups exhibited increased levels of the oxidative stress marker 4-hydroxynonenal in the striatum and SN, as well as the upregulation of the pro-apoptotic protein PKCδ and accumulation of glomerular astroglia in the OB. The co-exposure of animals to Mn/V resulted in higher levels of these metals compared to other treatment groups. Taken together, our results suggest that co-exposure to Mn/V can adversely affect the olfactory and nigral systems. These results highlight the possible role of environmental metal mixtures in the etiology of Parkinsonism.

Chamuangone-enriched rice bran oil ameliorates neurodegeneration in haloperidol-induced Parkinsonian rat model via modulation of neuro-inflammatory mediators and suppression of oxidative stress markers

A natural bioactive compound chamuangone extracted from Thai salad Garcinia cowa leaves exhibited robust medicinal properties, targeting central oxidative stress pathways, and having neuroprotective potential. Chamuangone-enriched rice bran oil (CERBO), with 1.97 mg/mL chamuangone, was obtained through green extraction. The study was designed to evaluate the anti-Parkinson’s activity of CERBO in the haloperidol- induced Parkinsonian rat model. Animals were categorized into six groups as control, disease control and treatment groups. Parkinson’s disease (PD)-like symptoms were induced by administration of haloperidol 1 mg/kg, intraperitoneally; CERBO treatment groups received 2.5, 5, and 7.5 mg/kg orally before the administration of haloperidol for 21 days. Neurobehavioral, biochemical, neurochemical, and histopathological studies along with gene expression analysis were performed at the completion of the study. CERBO markedly recover the motor and non-motor PD-like symptoms in treatment groups dose-dependently. The levels of antioxidant enzymes, such as catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase, increased, while malondialdehyde levels decreased dose-dependently in CERBO-treated groups. CERBO dose-dependent elevations were observed in neurotransmitters (dopamine, serotonin, and noradrenaline). PD-associated specific biomarker (α-synuclein) decreased dose-dependently with downregulation in messenger RNA expression of neuro-inflammatory mediators (interleukin α, interleukin 1β, and tumor necrosis factor-α). Histopathological studies revealed recovery in neuronal loss, formation of Lewy’s bodies, and neurofibrillary tangles in the treatment groups. It was concluded from the data that CERBO possessed good anti-Parkinson’s activity and could be a novel, safe, and effective remedy for the treatment of PD.

Spectrophotometric Study of Excitatory Amino Acids with Ortho-Phthalaldehyde

Background: Understanding the concentration of amino acids in biological samples is pivotal for numerous biochemical and clinical studies. Aspartic acid and glutamic acid, being excitatory amino acids, play crucial roles in the neurotransmission processes of the mammalian brain. Their precise quantification is essential for advancing our knowledge in neurochemistry and for the diagnosis of related disorders. Objective: This study aimed to develop a robust, accurate, and sensitive spectrophotometric method for quantifying aspartic and glutamic acids in solution, both in their native forms and when complexed with ortho-phthalaldehyde (OPA), a derivatization agent that enhances their absorbance properties. Methods: Utilizing a double-beam Hitachi 220 Spectrophotometer equipped with dual 1 cm silica cuvettes, we performed spectrophotometric analyses across a wavelength range of 165 to 1000 nm. Calibration curves for aspartic acid and glutamic acid, with and without OPA, were generated by plotting absorbance against concentration. Various solvents including methanol, ethanol, acetone, and acetonitrile were evaluated for their efficacy in dissolving the amino acids and their complexes. Linear regression analysis was employed to establish the relationship between concentration and absorbance, and the method's precision and accuracy were validated through replicate measurements at multiple concentrations. Results: The calibration curves exhibited excellent linearity for both amino acids, with and without OPA, across the tested concentration ranges. For aspartic acid, absorption maxima were observed at 201 nm (106,333.33 L mol^-1 cm^-1 molar absorptivity) and 229 nm (71,250 L mol^-1 cm^-1) for its OPA derivative. Glutamic acid showed absorption maxima at 198 nm (84,333.33 L mol^-1 cm^-1) and 216 nm (128,857.14 L mol^-1 cm^-1) for its OPA derivative. The correlation coefficients (R²) for the calibration curves ranged from 0.9954 to 0.9982, indicating a high degree of linearity and reliability of the method. Conclusion: The developed spectrophotometric method provides a reliable, precise, and sensitive approach for quantifying aspartic and glutamic acids. Its application is significant for biochemical analysis and has potential implications in clinical diagnostics, offering a promising tool for neurochemical studies.

“Correlation does not Imply Causation”, while Psychotropic Drugs do cause Neurochemical Imbalances and Dysfunction of Neurotransmission

Mental health professionals often prescribe psychotropic drugs to patients diagnosed with mental health illnesses under the premise that neurochemical imbalance is a main underlying cause of mental health disorders. In this paper we discuss reasons to believe that there is no scientific research which provides evidence that neurochemical imbalances or problems with neurotransmission in the brain are causative factors in the etiology of mental health illnesses. Behavioral and neurochemical research studies in animals show an ASSOCIATION between mental health states and alteration of neurotransmitter signaling. However, correlation does not imply causation. To the contrary, stress paradigms in rodents show a diminishing of the activity of the mesolimbic dopaminergic reward pathway _as a result of_ long-term stressful stimuli. Furthermore, studies in human cases of mental health disorders show that psychotropic drugs cause disturbances in neurotransmission or neurochemical homeostasis as seen in biochemical research studies, and this is manifest by the behavioral consequences experienced during withdrawal in humans and animals. SIGNIFICANCE: This paper presents reasons to question the safety and efficacy of the common use of psychotropic drugs in the mental health industry.

“Correlation does not Imply Causation”, while Psychotropic Drugs do cause Neurochemical Imbalances and Dysfunction of Neurotransmission

Mental health professionals often prescribe psychotropic drug to patients diagnosed with mental health illnesses under the premise that neurochemical imbalance is a cause of mental health disorders. In this paper we discuss reasons to believe that there is no scientific research which provides evidence that neurochemical imbalances or problems with neurotransmission in the brain are causative factors in the etiology of mental health illnesses. Behavioral and neurochemical research studies in animals show an ASSOCIATION between mental health states and alteration of neurotransmitter signaling. However, correlation does not imply causation. To the contrary, stress paradigms in rodents show a diminishing of the activity of the mesolimbic dopaminergic reward pathway _as a result of_ long-term stressful stimuli. Furthermore, studies in human cases of mental health disorders show that psychotropic drugs cause disturbances in neurotransmission or neurochemical homeostasis as seen in biochemical research studies, and this is manifest by the behavioral consequences experienced during withdrawal in humans and animals. SIGNIFICANCE: This paper presents reasons to question the safety and efficacy of the common use of psychotropic drugs in the mental health industry.

Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study.

The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin's effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.

Protective effects of niacin following high fat rich diet: an in-vivo and in-silico study

Niacin had long been understood as an antioxidant. There were reports that high fat diet (HFD) may cause psychological and physical impairments. The present study was aimed to experience the effect of Niacin on % growth rate, cumulative food intake, motor activity and anxiety profile, redox status, 5-HT metabolism and brain histopathology in rats. Rats were administered with Niacin at a dose of 50 mg/ml/kg body weight for 4 weeks following normal diet (ND) and HFD. Behavioral tests were performed after 4 weeks. Animals were sacrificed to collect brain samples. Biochemical, neurochemical and histopathological studies were performed. HFD increased food intake and body weight. The exploratory activity was reduced and anxiety like behavior was observed in HFD treated animals. Activity of antioxidant enzymes was decreased while oxidative stress marker and serotonin metabolism in the brain of rat were increased in HFD treated animals than ND fed rats. Morphology of the brain was also altered by HFD administration. Conversely, Niacin treated animals decreased food intake and % growth rate, increased exploratory activity, produced anxiolytic effects, decreased oxidative stress and increased antioxidant enzyme and 5-HT levels following HFD. Morphology of brain is also normalized by the treatment of Niacin following HFD. In-silico studies showed that Niacin has a potential binding affinity with degradative enzyme of 5-HT i.e. monoamine oxidase (MAO) A and B with an energy of ~ − 4.5 and − 5.0 kcal/mol respectively. In conclusion, the present study showed that Niacin enhanced motor activity, produced anxiolytic effect, and reduced oxidative stress, appetite, growth rate, increased antioxidant enzymes and normalized serotonin system and brain morphology following HFD intake. In-silico studies suggested that increase 5-HT was associated with the binding of MAO with Niacin subsequentially an inhibition of the degradation of monoamine. It is suggested that Niacin has a great antioxidant potential and could be a good therapy for the treatment of HFD induced obesity.

Binge-like administration of alcohol mixed to energy drinks to male adolescent rats severely impacts on mesocortical dopaminergic function in adulthood: A behavioral, neurochemical and electrophysiological study

A growing body of evidence indicates that the practice of consuming alcohol mixed with energy drinks (ED) (AMED) in a binge drinking pattern is significantly diffusing among the adolescent population. This behavior, aimed at increasing the intake of alcohol, raises serious concerns about its long-term effects. Epidemiological studies suggest that AMED consumption might increase vulnerability to alcohol abuse and have a gating effect on the use of illicit drugs.The medial prefrontal cortex (mPFC) is involved in the modulation of the reinforcing effects of alcohol and of impulsive behavior and plays a key role in the development of addiction. In our study, we used a binge-like protocol of administration of alcohol, ED, or AMED in male adolescent rats, to mimic the binge-like intake behavior observed in humans, in order to evaluate whether these treatments could differentially affect the function of mesocortical dopaminergic neurons in adulthood. We did so by measuring: i) physiological sensorimotor gating; ii) voluntary alcohol consumption and dopamine transmission before, during, and after presentation of alcohol; iii) electrophysiological activity of VTA dopaminergic neurons and their sensitivity to a challenge with alcohol. Our results indicate that exposure to alcohol, ED, or AMED during adolescence induces differential adaptive changes in the function of mesocortical dopaminergic neurons and, in particular, that AMED exposure decreases their sensitivity to external stimuli, possibly laying the foundation for the altered behaviors observed in adulthood.

Disposable facemask waste combustion emits neuroactive smoke particulate matter

Tremendous deposits of disposable medical facemask waste after the COVID-19 pandemic require improvement of waste management practice according to WHO report 2022, moreover facemasks are still in use around the world to protect against numerous airborne infections. Here, water-suspended smoke preparations from the combustion of disposable medical facemasks (polypropylene fibers) were collected; size, zeta potential, surface groups of smoke particulate matter were determined by dynamic light scattering, FTIR and Raman spectroscopy, and their optical properties were characterized. Neurochemical study using nerve terminals isolated from rat cortex revealed a significant decrease in the initial rate of the uptake/accumulation of excitatory and inhibitory neurotransmitters, L-[14C]glutamate and [3H]GABA, and exocytotic release, and also an increase in the extracellular level of these neurotransmitters. Fluorescent measurements revealed that ROS generation induced by hydrogen peroxide and glutamate receptor agonist kainate decreased in nerve terminals. A decrease in the membrane potential of nerve terminals and isolated neurons, the mitochondrial potential and synaptic vesicle acidification was also shown. Therefore, accidental or intentional utilization of disposable medical facemask waste by combustion results in the release of neuroactive ultrafine particulate matter to the environment, thereby contributing to plastic-associated pollution of air and water resources and neuropathology development and expansion.

Altered brain dopamine metabolism is a trait marker for bipolar disorder

Pharmacological treatment, imaging, and neurochemistry studies identify altered dopamine signaling in bipolar disorder. Our previous work has shown higher concentration of homovanillic acid (HVA), the end metabolite of dopamine, in cerebrospinal fluid (CSF) from individuals with bipolar disorder compared to healthy controls. Here, we analyzed HVA concentrations from a follow-up visit in 103 adults with bipolar disorder and 57 controls from our first cohort. Further, we analyzed CSF monoamine metabolite concentrations in a second cohort of 152 adults with bipolar disorder and 55 controls. At the follow-up visit for the first cohort, HVA was higher in individuals with bipolar disorder (278 ± 102 nmol/L, p = 0.003) compared with controls (232 ± 83 nmol/L). In the second cohort, individuals with bipolar disorder had higher HVA (272 ± 97 nmol/L, p = 0.001) and lower 3-methoxy-4-hydroxyphenylglycol (MHPG, 40 ± 9 nmol/L, p = 0.002) concentrations than controls (HVA, 231 ± 71 nmol/L and MHPG, 45 ± 9 nmol/L). Baseline and follow-up measures of monoamine metabolites showed medium to high correlation to each other but did not predict course of illness. We failed to replicate the association of HVA concentration and psychotic symptoms but confirmed lower 5-hydroxyindoleacetic acid (5-HIAA) concentration in individuals treated with antidepressants. In conclusion, we confirmed high HVA concentration in CSF in patients with bipolar disorder compared to a control group. Previous work suggest that this is a feature shared with ADHD but distinct from schizophrenia and major depressive disorder. The role of increased HVA concentration in the course of illness in bipolar disorder remains unclear.

Effect of Quinolinic Acid on Behavior, Morphology, and Expression of Inflammatory/oxidative Status in Rats' Striatum: Is Coenzyme Q10 a Good Protector?

Quinolinic acid (QUIN) is a toxic compound with pro-oxidant, pro-inflammatory, and pro-apoptotic actions found at high levels in the central nervous system (CNS) in several pathological conditions. Due to the toxicity of QUIN, it is important to evaluate strategies to protect against the damage caused by this metabolite in the brain. In this context, coenzyme Q10 (CoQ10) is a provitamin present in the mitochondria with a protective role in cells through several mechanisms of action. Based on these, the present study was aimed at evaluating the possible neuroprotective role of CoQ10 against damage caused by QUIN in the striatum of young Wistar rats. Twenty-one-day-old rats underwent a 10-day pretreatment with CoQ10 or saline (control) intraperitoneal injections and on the 30th day of life received QUIN intrastriatal or saline (control) administration. The animals were submitted to behavior tests or euthanized, and the striatum was dissected to neurochemical studies. Results showed that CoQ10 was able to prevent behavioral changes (the open field, object recognition, and pole test tasks) and neurochemical parameters (alteration in the gene expression of IL-1β, IL-6, SOD, and GPx, as well as in the immunocontent of cytoplasmic Nrf2 and nuclear p-Nf-κβ) caused by QUIN. These findings demonstrate the promising therapeutic effects of CoQ10 against QUIN toxicity.

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System.

2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)_ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT (p-DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.

An Update on Apathy in Alzheimer's Disease.

Apathy is a complex multi-dimensional syndrome that affects up to 70% of individuals with Alzheimer's disease (AD). Whilst many frameworks to define apathy in AD exist, most include loss of motivation or goal-directed behaviour as the central feature. Apathy is associated with significant impact on persons living with AD and their caregivers and is also associated with accelerated cognitive decline across the AD spectrum. Neuroimaging studies have highlighted a key role of fronto-striatial circuitry including the anterior cingulate cortex (ACC), orbito-frontal cortex (OFC) and associated subcortical structures. Importantly, the presence and severity of apathy strongly correlates with AD stage and neuropathological biomarkers of amyloid and tau pathology. Following from neurochemistry studies demonstrating a central role of biogenic amine neurotransmission in apathy syndrome in AD, recent clinical trial data suggest that apathy symptoms may improve following treatment with agents such as methylphenidate-which may have an important role alongside emerging non-pharmacological treatment strategies. Here, we review the diagnostic criteria, rating scales, prevalence, and risk factors for apathy in AD. The underlying neurobiology, neuropsychology and associated neuroimaging findings are reviewed in detail. Finally, we discuss current treatment approaches and strategies aimed at targeting apathy syndrome in AD, highlighting areas for future research and clinical trials in patient cohorts.

The role of the anterior cingulate cortex in aggression and impulsivity.

Aggression is a complex social behavior that evolved in the context of defending a territory, fighting for limited resources, and competing for mates and protection. Although aggression considered as a negative or undesirable emotion is an essential part of many species' repertoire of social behaviors. For humans, the motivations, actions, and limits of aggressive acts are not always clear. However, uncontrolled aggression may have destructive consequences, and it develops inappropriately into violence. At the neural level, several studies demonstrated that aggression is related to cortical abnormalities, including the anterior cingulate cortex (ACC). This review summarizes the state of the literature regarding the involvement of ACC in the neurobiology of aggression and impulsivity. We will first review structural and neuroanatomical studies, including volumetric and functional investigations of aggression. Next, we will discuss the neurochemical and neuropharmacological studies of aggression related to the ACC. We will focus mainly on the gamma-aminobutyric acid/glutamate balance, as well as the serotoninergic system. Finally, we will try to integrate these results and reconcile discrepancies in the field and suggest recommendations for future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).