Neurochemical Research最新文献

{"title":"Acute Behavioral and Neurochemical Effects of Sulpiride in Adult Zebrafish","authors":"David S. Galstyan,&nbsp;Andrey S. Lebedev,&nbsp;Nikita P. Ilyin,&nbsp;Maria S. Papulova,&nbsp;Nikita I. Golushko,&nbsp;Valeria V. Tishkina,&nbsp;Daryna K. Saklakova,&nbsp;Daniil Martynov,&nbsp;Tatiana O. Kolesnikova,&nbsp;Dennis B. Rosemberg,&nbsp;Murilo S. De Abreu,&nbsp;Konstantin A. Demin,&nbsp;Allan V. Kalueff","doi":"10.1007/s11064-024-04268-9","DOIUrl":"10.1007/s11064-024-04268-9","url":null,"abstract":"<div><p>Affective and psychotic disorders are highly prevalent and severely debilitating mental illnesses that often remain untreated or treatment-resistant. Sulpiride is a common antipsychotic (neuroleptic) drug whose well-established additional (e.g., antidepressant) therapeutic effects call for further studies of a wider spectrum of its CNS effects. Here, we examined effects of acute 20-min exposure to sulpiride (50–200 mg/L) on anxiety- and depression-like behaviors, as well as on brain monoamines, in adult zebrafish (<i>Danio rerio</i>). Overall, sulpiride exerted overt anxiolytic-like effects in the novel tank test and showed tranquilizing-like effects in the zebrafish tail immobilization test, accompanied by lowered whole-brain dopamine and its elevated turnover, without affecting serotonin or norepinephrine levels and their turnover. Taken together, these findings support complex behavioral pharmacology of sulpiride in vivo and reconfirm high sensitivity of zebrafish-based screens to this and, likely, other related clinically active neuroleptics.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction","authors":"Yuanfei Luo,&nbsp;Linying Yuan,&nbsp;Zhihui Liu,&nbsp;Weichen Dong,&nbsp;Li Huang,&nbsp;Anyu Liao,&nbsp;Yi Xie,&nbsp;Rui Liu,&nbsp;Wenya Lan,&nbsp;Yulong Cai,&nbsp;Wusheng Zhu","doi":"10.1007/s11064-024-04272-z","DOIUrl":"10.1007/s11064-024-04272-z","url":null,"abstract":"<div><p>Proprotein convertase substilin/kexin type 9 (PCSK9), a pivotal protein regulating lipid metabolism, has been implicated in promoting microthrombotic formation and inflammatory cascades, thereby contributing to cardiovascular ischemia/reperfusion (I/R) injury. However, its involvement in cerebral I/R injury and its potential role in microcirculation protection remain unexplored. In this investigation, we utilized a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate ischemic stroke. Different concentrations of evolocumab (1, 5, 10 mg/kg, i.v.), a PCSK9 inhibitor, were administered to assess its impact. Immunofluorescence staining was employed to analyze changes in the expression of occludin, claudin-5, thrombocyte, ICAM-1, VCAM-1, and CD45, providing insights into blood-brain barrier integrity, platelet adhesion, and immune cell infiltration. Moreover, the Morris water maze and elevated plus maze were utilized to evaluate neurological and behavioral functions in MCAO/R mice, shedding light on the effects of PCSK9 inhibition. Our findings revealed a surge in plasma PCSK9 levels post-MCAO/R, peaking at 24 h post-reperfusion. Evolocumab (10 mg/kg) treatment significantly mitigated brain infarction and neurological deficits, evidenced by enhanced locomotor function and reduced post-stroke anxiety. However, it did not ameliorate cognitive impairment following MCAO/R. Additionally, evolocumab administration led to diminished leakage of evans blue solution and upregulated expression of occludin and claudin-5. Thrombocyte, ICAM-1, VCAM-1, and CD45 levels were notably reduced in the penumbral area post-evolocumab treatment. These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP Restoration by ATP-Deprived Cultured Primary Astrocytes","authors":"Gabriele Karger,&nbsp;Johanna Elisabeth Willker,&nbsp;Antonia Regina Harders,&nbsp;Patrick Watermann,&nbsp;Ralf Dringen","doi":"10.1007/s11064-024-04276-9","DOIUrl":"10.1007/s11064-024-04276-9","url":null,"abstract":"<div><p>A high cellular concentration of adenosine triphosphate (ATP) is essential to fuel many important functions of brain astrocytes. Although cellular ATP depletion has frequently been reported for astrocytes, little is known on the metabolic pathways that contribute to ATP restoration by ATP-depleted astrocytes. Incubation of cultured primary rat astrocytes in glucose-free buffer for 60 min with the mitochondrial uncoupler BAM15 lowered the cellular ATP content by around 70%, the total amount of adenosine phosphates by around 50% and the adenylate energy charge (AEC) from 0.9 to 0.6. Testing for ATP restoration after removal of the uncoupler revealed that the presence of glucose as exclusive substrate allowed the cells to restore within 6 h around 80% of the initial ATP content, while coapplication of adenosine plus glucose enabled the cells to fully restore their initial ATP content within 60 min. A rapid but incomplete and transient ATP restoration was found for astrocytes that had been exposed to adenosine alone. This restoration was completely prevented by application of the pyruvate uptake inhibitor UK5099, the respiratory chain inhibitor antimycin A or by the continuous presence of BAM15. However, the presence of these compounds strongly accelerated the release of lactate from the cells, suggesting that the ribose moiety of adenosine can serve as substrate to fuel some ATP restoration via mitochondrial metabolism. Finally, the adenosine-accelerated ATP restoration in glucose-fed astrocytes was inhibited by the presence of the adenosine kinase inhibitor ABT-702. These data demonstrate that astrocytes require for a rapid and complete ATP restoration the presence of both glucose as substrate and adenosine as AMP precursor.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04276-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morin Ameliorates Lipopolysaccharides-Induced Sepsis-Associated Encephalopathy and Cognitive Impairment in Albino Mice","authors":"Asmaa R. Mohamed,&nbsp;Nagui H. Fares,&nbsp;Yomna I. Mahmoud","doi":"10.1007/s11064-024-04269-8","DOIUrl":"10.1007/s11064-024-04269-8","url":null,"abstract":"<div><p>Sepsis-associated encephalopathy is a common neurological complication of sepsis that is characterized by neuroinflammation, oxidative stress and apoptosis, which results in cognitive impairments in septic survivors. Despite numerous treatment options for this condition, none of them are definite. Therefore, this study aimed to investigate the impact of morin, a flavone known for its neuroprotective and anti-inflammatory effects, against lipopolysaccharides-induced sepsis-associated encephalopathy in albino mice for 7 days. Mice were divided into 4 groups: Negative control, morin, septic, and septic morin-treated mice. Sepsis was induced by a single injection of lipopolysaccharides (5 mg/kg, intraperitoneally), morin (50 mg/kg b. wt.) was given orally, starting from 5 h after sepsis induction, then daily for 4 other days. Morin ameliorated septic structural and functional alternations as manifested by improving the survival rate, the behavioral functions, in addition to preserving and protecting the brain tissue. This was accompanied with the augmentation of the total antioxidant capacity, as well as the suppression of tissue levels of the lipid peroxidation marker malondialdehyde, apoptosis (cleaved-caspase-3), glial fibrillary acidic protein, and the proinflammatory cytokine tumor necrosis factor. In conclusion, morin has a promising ameliorative effect to counteract the sepsis-associated encephalopathy via its anti-inflammatory and antioxidant effects and to prevent the associated cognitive impairments.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04269-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lentivirus-mediated Knockdown of Ski Improves Neurological Function After Spinal Cord Injury in Rats","authors":"Zhi-Qiang Wang,&nbsp;Rui Ran,&nbsp;Chun-Wei Ma,&nbsp;Guang-Hai Zhao,&nbsp;Kai-Sheng Zhou,&nbsp;Hai-Hong Zhang","doi":"10.1007/s11064-024-04261-2","DOIUrl":"10.1007/s11064-024-04261-2","url":null,"abstract":"<div><p>The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and neurological function after spinal cord injury, we prepared a rat spinal cord injury model using Allen’s percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly suppressed the expression of glial fibrillary acidic protein (Gfap) and vimentin, hallmark molecules of glial scarring, and increased the expression of neurofilament protein-200 (Nf-200) and growth-associated protein (Gap43), key molecules of axon regeneration, as well as Synaptophysin, a key molecule of synapse formation expression. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results suggest that Ski is able to inhibit the expression of key molecules of glial scar formation, and at the same time promotes the expression of molecules that are markers of axonal regeneration and synapse formation after spinal cord injury, making it a potential target for targeted therapy after spinal cord injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Enhances the Efficacy of Combined BM-MSCs Therapy for Rat Spinal Cord Injury via Modulation of the Sirt-1/NF-κB Signaling Pathway","authors":"Hao Chen,&nbsp;Haosen Zhao","doi":"10.1007/s11064-024-04264-z","DOIUrl":"10.1007/s11064-024-04264-z","url":null,"abstract":"<div><p>Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Monitoring of Glutathione Stability in Different Microenvironments","authors":"Yashika Arora,&nbsp;Avantika Samkaria,&nbsp;Joseph C. Maroon,&nbsp;Pravat K. Mandal","doi":"10.1007/s11064-024-04265-y","DOIUrl":"10.1007/s11064-024-04265-y","url":null,"abstract":"<div><p>Glutathione (GSH) is a master antioxidant which primarily protects cells from oxidative stress. Clinical studies have found significant depletion of GSH from the hippocampus in patients with mild cognitive impairment (MCI), a transitional stage before conversion to Alzheimer’s disease (AD). Significant depletion of GSH is considered an early diagnostic biomarker of AD. Postmortem studies have confirmed significant GSH depletion in hippocampal tissue in MCI patients. The stability of GSH in different microenvironments is essential to validate GSH as a reliable biomarker for AD. Accordingly, we have conducted longitudinal monitoring of GSH from various brain regions (frontal cortex (FC), parietal cortex (PC), occipital cortex (OC), and cerebellum (CER)) from healthy subjects using MEshcher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) pulse sequence on a 3T scanner. Additionally, in vitro magnetic resonance spectroscopy (MRS) assessments were conducted longitudinally using the same study protocol involving GSH supplement in a physiologically relevant phosphate buffer solution (PBS). We report that GSH within the brain microenvironment of a healthy person remains stable over time. GSH, however, is susceptible to oxidation over time in a phosphate buffer environment. The stability of GSH in a longitudinal study in the brains of healthy individuals supports the consideration of GSH as a candidate for stable biomarker for AD.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04265-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of JM-20 on Age-Related Cognitive Impairment in Mice","authors":"Maylin Wong-Guerra,&nbsp;Yanay Montano-Peguero,&nbsp;Jeney Ramírez-Sánchez,&nbsp;Enrique García Alfonso,&nbsp;Daniela Hernández-Enseñat,&nbsp;Yeniceis Alcántara Isaac,&nbsp;Alejandro Saúl Padrón-Yaquis,&nbsp;João Batista Teixeira da Rocha,&nbsp;Luis Arturo Fonseca-Fonseca,&nbsp;Yanier Núñez-Figueredo","doi":"10.1007/s11064-024-04254-1","DOIUrl":"10.1007/s11064-024-04254-1","url":null,"abstract":"<div><p>The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer’s disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8 mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8 mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20-Hydroxyeicosatetraenoic Acid Regulates the Src/EGFR/NF-κB Signaling Pathway Via GPR75 to Activate Microglia and Promote TBI in the Immature Brain","authors":"Zhihui Ma,&nbsp;Yalei Ning,&nbsp;Xiaoli Chen,&nbsp;Shan Zhao,&nbsp;Jie Yan,&nbsp;Bo Wang,&nbsp;Changhong Li,&nbsp;Ruobing Gao,&nbsp;Xing Chen,&nbsp;Nan Yang,&nbsp;Yan Peng,&nbsp;Ping Li,&nbsp;Shiyu Shu","doi":"10.1007/s11064-024-04260-3","DOIUrl":"10.1007/s11064-024-04260-3","url":null,"abstract":"<div><p>20-Hydroxyeicosatetraenoic acid (20-HETE) is associated with secondary damage in traumatic brain injury (TBI) of the immature brain. Microglial activation is pivotal in this process. However, the underlying mechanism of action remains unknown. While 20-HETE interacts with G protein-coupled receptor 75 (GPR75) in some pathological processes, their interaction in brain tissue remains uncertain. This study aimed to investigate whether 20-HETE can activate microglia by binding to GPR75 in TBI of the immature brain. Drug affinity responsive molecular target stability (DARTS) assays, cycloheximide (CHX) chase assays, and auto-dock assays were employed to analyze the interaction between 20-HETE and GPR75. The expression levels of cytochrome P450 4A (CYP4A) and GPR75 in activated microglia in an immature brain TBI model were observed by western blot and multiple immunofluorescence staining. The effects of different levels of 20-HETE expression and lentivirus-mediated GPR75 gene silencing on 20-HETE-induced inflammatory factor release from BV-2 cells were observed by enzyme-linked immunoassay (ELISA). The phosphorylation levels of the downstream Src kinase, epidermal growth factor receptor (EGFR), and nuclear factor (NF)-κB were assessed using western blot. Cell viability and apoptosis were detected by CCK-8 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. 20-HETE bound to the GPR75 protein and inhibited its degradation. GPR75 gene silencing reversed the 20-HETE-induced inflammatory activation of BV-2 cells, effectively inhibiting the activation of the Src/EGFR/NF-κB pathway and the effects of 20-HETE on cell viability and the apoptosis rate. In contrast, overexpression of GPR75 had the opposite effect. In addition, after immature brain TBI, the 20-HETE and GPR75 expression levels were upregulated in microglia, with significant activation of the Src/EGFR/NF-κB pathway. Inhibition of 20-HETE synthesis with N-hydroxy-N’-(4-n-butyl-2-methylphenyl) formamidine (HET0016) produced the opposite effect. 20-HETE regulates the Src/EGFR/NF-κB signaling pathway via GPR75 to activate microglia, promoting immature brain TBI. These findings offer a novel target for promoting the brain injury effect of 20-HETE.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Acute Haloperidol Treatment on Dopaminergic Markers, GAD67, and A2A Receptors in Rats with High and Low VCMs","authors":"Getulio Nicola Bressan,&nbsp;Talita Rodrigues,&nbsp;Maria Eduarda Brandli da Silva,&nbsp;Maria Rosa Chitolina Schetinger,&nbsp;Rahisa Scussel,&nbsp;Ricardo Andrez Machado-de-Ávila,&nbsp;Jéssica da Silva Abel,&nbsp;Roselei Fachinetto","doi":"10.1007/s11064-024-04275-w","DOIUrl":"10.1007/s11064-024-04275-w","url":null,"abstract":"<div><p>Vacuous chewing movements (VCM) have been utilized as an experimental model of orofacial dyskinesia (OD) in rodents to study the underlying molecular mechanisms related to tardive dyskinesia (TD). This study aimed to investigate if the acute treatment with haloperidol can alter components of the dopaminergic synapse or its modulators such as glutamic acid decarboxylase (GAD₆₇) and adenosine 2A (A_2A) receptor. Furthermore, to evaluate if changes in molecular markers are associated with the number of VCMs induced by haloperidol in rats it is proposing a method to classify the animals into High and Low VCM groups. Here, we treated rats with haloperidol decanoate (single injection, intramuscularly, 28 mg/Kg of unconjugated haloperidol) and evaluated the number of VCMs after 4 weeks. Haloperidol-treated rats were divided into three groups (Low, High, and Spontaneous VCM) according to the evaluation of the VCM profile proposed here. After, dopamine (DA) levels, monoamine oxidase (MAO) activity, and the immunoreactivity of tyrosine hydroxylase (TH), dopamine transporter (DAT), D₂ receptor, GAD₆₇, and A_2A were determined in brain structures. No significant differences were found in DA levels, MAO activity, and immunoreactivity of the TH, DAT, D₂ receptor, GAD₆₇, and A_2A receptor in brain structures. VCM intensity was correlated with TH immunoreactivity in <i>Sn</i> in the High VCM group while it was inversely correlated with the immunoreactivity of the A_2A receptor in the striatum of the Spontaneous VCM group. Other significant correlations were found considering the VCM profile suggesting that High VCM after acute haloperidol treatment seems to be associated with the lack of ability to reorganize the neurotransmission in the nigrostriatal pathway. Further studies could clarify the main targets involved in the motor side effects of antipsychotics. The present study demonstrated an easy way to separate the animals into High and Low VCMs.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}