Brain Research最新文献

{"title":"The effect of Naringin on cognitive function, oxidative stress, cholinergic activity, CREB/BDNF signaling and hippocampal cell damage in offspring rats with utero-placental insufficiency-induced intrauterine growth restriction","authors":"Samireh Nemati ,&nbsp;Mohammad Amin Edalatmanesh ,&nbsp;Mohsen Forouzanfar","doi":"10.1016/j.brainres.2025.149448","DOIUrl":"10.1016/j.brainres.2025.149448","url":null,"abstract":"<div><div>Intrauterine growth restriction (IUGR) induced by utero-placental insufficiency (UPI) results in delayed neural development and impaired brain growth. This study investigates the effects of Naringin (Nar) on memory, learning, cholinergic activity, oxidative stress markers, hippocampal CREB/BDNF signal pathway and cell damage in offspring of rats exposed to UPI. Twenty pregnant Wistar rats were randomly assigned to four groups: control, sham surgery, UPI + NS (UPI + normal saline as a vehicle), and UPI + Nar (UPI + Nar at 100 mg/kg/day). UPI was induced by permanently occluding the uterine anterior vessels on embryonic day (ED) 18. Naringin or saline was administered orally from ED15 to ED21. Behavioral assessments of offspring, including working memory, avoidance learning, and anxiety-like behavior, were conducted on a postnatal day (PND) 21. Subsequently, hippocampal acetylcholinesterase (AChE) activity, catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), hippocampal transcript level of cyclic AMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) and apoptotic neuron density in the hippocampus were evaluated. Naringin-treated rats demonstrated significant improvements in working and avoidance memory, increases in CAT, SOD, and TAC, CREB, BDNF and reductions in AChE activity, MDA levels, apoptotic neuron density, and anxiety-like behaviors compared to the UPI + NS group (<em>p &lt; 0.05</em>). Naringin mitigates hippocampal cell damage, cognitive impairments, and anxiety by enhancing antioxidant defenses, modulating cholinergic activity and CREB/BDNF signaling in the brains of UPI-exposed offspring.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149448"},"PeriodicalIF":2.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A non-purine inhibitor of xanthine oxidoreductase mitigates adenosine triphosphate degradation under hypoxic conditions in mouse brain","authors":"Nana Sato ,&nbsp;Teruo Kusano ,&nbsp;Koji Nagata ,&nbsp;Ken Okamoto","doi":"10.1016/j.brainres.2025.149444","DOIUrl":"10.1016/j.brainres.2025.149444","url":null,"abstract":"<div><div>The brain is an organ that consumes a substantial amount of oxygen, and a reduction in oxygen concentration can rapidly lead to significant and irreversible brain injury. The progression of brain injury during hypoxia involves the depletion of intracellular adenosine triphosphate (ATP) due to decreased oxidative phosphorylation in the inner mitochondrial membrane. Allopurinol is a purine analog inhibitor of xanthine oxidoreductase that protects against hypoxic/ischemic brain injury; however, its underlying mechanism of action remains unclear. In addition, febuxostat is a non-purine xanthine oxidoreductase inhibitor with a different inhibitory mechanism from allopurinol. The impact of febuxostat on brain injury has not been well investigated. Therefore, this study aimed to examine brain ATP and its catabolite levels in the presence or absence of allopurinol and febuxostat under hypoxic conditions by inactivating brain metabolism using focal microwave irradiation. The hypoxic treatment caused a decrease in the adenylate energy charge and ATP levels and an increase in its catabolic products in mouse brains. The febuxostat group showed higher energy charge and ATP levels and lower ATP catabolites than the control group. Notably, despite the comparable suppression of uric acid production in both inhibitor groups, allopurinol treatment was less effective than febuxostat. These results suggest that febuxostat effectively prevents hypoxia-induced ATP degradation in the brain and that its effect is more potent than allopurinol. This study will contribute to developing therapies for improving hypoxia-induced brain dysfunction.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149444"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the appropriate measurement environment for laser speckle flowmetry of cerebral blood flow in rats","authors":"Ryosei Wakasa,&nbsp;Takahiro Ono,&nbsp;Naomoto Senbokuya,&nbsp;Mikiko Kuwayama,&nbsp;Hiroaki Shimizu","doi":"10.1016/j.brainres.2025.149443","DOIUrl":"10.1016/j.brainres.2025.149443","url":null,"abstract":"<div><div>Laser speckle flowmetry (LSF) is a noninvasive tool for cerebral blood flow (CBF) measurement via a cranial bone window. LSF is influenced by various factors including the extent of removal of bone and dura mater and tissue wetness in the bone window. In this study, we aimed to characterize the effect of these conditions on LSF signals and identify optimal measurement conditions for CBF LSF measurements in rats. Three bone windows were created over the Sprague-Dawley rat brains including (i) bone removal until the brain surface was visible through the thin skull, (ii) complete bone removal for dura mater exposure, and (iii) dura mater removal for cortical surface exposure. We investigated the difference in the LSF signals of these windows under dry and wet conditions. The differences between signals obtained using artificial cerebrospinal fluid (aCSF) and mineral oil for wet conditions were also examined. Furthermore, we investigated the stability of repeated CBF measurements in thinned skulls over 15 days and the effects of gentamicin ointment. No significant difference was observed in the LSF values of the three bone windows under dry and wet conditions. Moreover, mineral oil may provide better LSF signal stability. CBF LSF measurements with minimum signal fluctuation were possible for 15 days using the thinned skull window with gentamicin ointment. In conclusion, CBF LSF measurements are feasible in rats using thinned skulls or dura matter in dry or wet environments, preferably with mineral oils. Relatively repetitive CBF LSF measurements were possible for long duration using gentamicin ointment for daily wound closure.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149443"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal protective effect of Artemisinin in ischemic stroke: Achieved by blocking lysine demethylase 1A-mediated demethylation of sphingosine kinase 2","authors":"He Li ,&nbsp;Ying Li ,&nbsp;Yingju Wang ,&nbsp;Yuchen Sheng","doi":"10.1016/j.brainres.2024.149442","DOIUrl":"10.1016/j.brainres.2024.149442","url":null,"abstract":"<div><div>Artemisinin (ART), a natural product isolated from the traditional Chinese plant <em>Artemisia annua</em> L., has shown neuroprotective properties in addition to its well-established antimalarial activities. This study investigates the therapeutic effect of ART in ischemic stroke (IS) and delves into its functional mechanism. Bioinformatics analyses revealed lysine demethylase 1A (KDM1A) as a promising target of ART aberrantly overexpressed in the context of IS. Increased KDM1A expression was detected in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated hippocampal neurons and transient middle cerebral artery occlusion (tMCAO)-challenged mice. Treatment with ART reduced KDM1A protein level, thus protecting mouse hippocampal neurons from OGD/R-induced oxidative stress and apoptosis. <em>In vivo</em>, ART reduced infarct size, reduced brain content, enhanced neurological function, and enhanced neuronal survival in tMCAO. Regarding the downstream cascade, KDM1A was found to repress transcription of sphingosine kinase 2 (SPHK2) by removing H3K4me2 modification near the SPHK2 promoter. Either KDM1A overexpression or SPHK2 knockdown abrogated the neuroprotective effects of ART. The ample evidence of this study suggests that ART fulfills neuroprotective functions in the context of IS by protecting SPHK2 from KDM1A-mediated transcription repression, highlighting ART as a promising regimen for the treatment of IS.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149442"},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HD-tACS over the left frontal aslant tract entrains theta activity associated with speech motor control","authors":"Karim Johari,&nbsp;Fatemeh Tabari","doi":"10.1016/j.brainres.2024.149434","DOIUrl":"10.1016/j.brainres.2024.149434","url":null,"abstract":"<div><div>Transient disruption or permanent damage to the left Frontal Aslant Tract (FAT) is associated with deficits in speech production. The present study examined the application of theta (4 Hz) high-definition transcranial alternating current stimulation (HD-tACS) over the left SMA and IFG –as a part of FAT- as a potential multisite protocol to modulate neural and behavioral correlates of speech motor control. Twenty-one young adults participated in three counterbalanced sessions in which they received in-phase, anti-phase, and sham theta HD-tACS. In each session, 4 Hz stimulation was applied over the left IFG and SMA, and subsequently EEG data was recorded while participants performed a speech Go/No-Go task. Relative to sham and anti-phase, in-phase HD-tACS significantly improved speech reaction time. Neural data showed an increase in the power of frontal theta activity prior to speech initiation for the in-phase condition compared to sham. Moreover, in-phase stimulation increased the phase synchrony of theta activity between the left central and frontal electrodes. For speech inhibition, the power of theta activity increased following the in-phase condition over frontocentral electrodes. Furthermore, the in-phase condition enhanced the connectivity between the left central and frontal electrodes. Overall findings suggest that in-phase theta HD-tACS of FAT enhanced the neural markers of cognitive control required for motor preparation and inhibition during a speech task and have translational implications.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149434"},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated non-hemorrhagic and non-contusional mild traumatic brain injury in rats elicits behavioral impairment with microglial activation, astrogliosis, and tauopathy: Reproducible and quantitative model of chronic traumatic encephalopathy","authors":"Chiaki Sugahara ,&nbsp;Kyohei Kin ,&nbsp;Tatsuya Sasaki ,&nbsp;Susumu Sasada ,&nbsp;Satoshi Kawauchi ,&nbsp;Satoru Yabuno ,&nbsp;Takayuki Nagase ,&nbsp;Takahiro Hirayama ,&nbsp;Kaori Masai ,&nbsp;Kakeru Hosomoto ,&nbsp;Yosuke Okazaki ,&nbsp;Koji Kawai ,&nbsp;Shun Tanimoto ,&nbsp;Yuichi Hirata ,&nbsp;Hayato Miyake ,&nbsp;Hiromichi Naito ,&nbsp;Takao Yasuhara ,&nbsp;Cesar V Borlongan ,&nbsp;Isao Date ,&nbsp;Shota Tanaka","doi":"10.1016/j.brainres.2024.149412","DOIUrl":"10.1016/j.brainres.2024.149412","url":null,"abstract":"<div><div>Chronic traumatic encephalopathy (CTE) has attracted attention due to sports-related head trauma or repetitive mild traumatic brain injury (mTBI). However, the pathology of CTE remains underexplored. Reproducible and quantitative model of CTE has yet to be established. The aim of this study is to establish a highly reproducible model of CTE with behavioral and histological manifestations. First, the pathological symptoms of mTBI with no intracranial hemorrhage or contusion using the weight drop model of 52 g ball from a height of 30 cm was determined using hematoxylin and eosin staining. Adult rats that received single, double, or triple head impacts were compared with sham behaviorally and histologically. Results revealed that rats exposed to repetitive mTBI showed motor impairment with gradual recovery over time, which was prolonged as the number of head impact increased. Similarly, cognitive function was impaired by repetitive mTBI and the recovery depended on the number of head impact. Histologically, GFAP positive astrocytes increased with repetitive mTBI, although Iba-1 positive microglial aggregation was limited. At 4w, phosphorylated Tau significantly accumulated in the prefrontal cortex, corpus callosum, CA1, and dentate gyrus of rats that received triple mTBI, compared to sham or those exposed to single, or double mTBI. This repetitive mTBI rat model provides a highly reproducible and quantifiable brain and behavioral pathology reminiscent of CTE.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149412"},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-N-Butylphthalide alleviate Aβ-induced cellular senescence through the CDK2-pRB1-Caspase3 axis","authors":"Yuanruhua Tian ,&nbsp;Wenke Li ,&nbsp;Yongbo Zhang","doi":"10.1016/j.brainres.2024.149435","DOIUrl":"10.1016/j.brainres.2024.149435","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) and leading to cellular senescence and cognitive deficits. Cellular senescence contributes significantly to the pathogenesis of AD through the senescence-associated secretory phenotype (SASP), exacerbating Aβ deposition. This study investigates the protective effects of 3-N-Butylphthalide (NBP), a compound derived from Apium graveolens Linn (Chinese celery), on Aβ-induced cellular senescence in U87 cells. Using RNA-sequencing and biochemical assays, we demonstrate that NBP ameliorate Aβ oligomer-induced cellular senescence and apoptosis, and regulated the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and components of the cyclin-dependent kinase 2 (CDK2)- phosphorylated retinoblastoma 1 (pRB1)-Caspase3 pathway. Moreover, NBP was shown to suppress the expression of SASP-related genes. These findings suggest that NBP rescues U87 cells from Aβ oligomer-induced senescence and apoptosis through modulating the CDK2-pRB1-Caspase3 axis and SASP expression. Our results underscore the potential of NBP as a senostatic agent for AD which have not been reported in previous studies, offering insights into its mechanisms of action and paving the way for future studies on its efficacy in vivo and in clinical settings. Thus, we contribute to growing evidence supporting the use of senolytic and senostatic agents in the treatment of AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149435"},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural remodeling of the brain cortex and functional recovery following hypoglossal-facial neurorrhaphy in patients with facial paralysis","authors":"Binbin Wang ,&nbsp;Miao Ling ,&nbsp;Chao Guo ,&nbsp;Shengqiao Sun ,&nbsp;Xingnan Zhang ,&nbsp;Chenhao Hu ,&nbsp;Hanjie Liu ,&nbsp;Dezhi Li ,&nbsp;Michael Schumacher ,&nbsp;Binbin Sui ,&nbsp;Song Liu","doi":"10.1016/j.brainres.2024.149437","DOIUrl":"10.1016/j.brainres.2024.149437","url":null,"abstract":"<div><h3>Objective</h3><div>Peripheral nerve injury results in functional alterations of the corresponding active brain areas, which are closely related to functional recovery. Whether such functional plasticity induces relative anatomical structural changes remains to be investigated.</div></div><div><h3>Methods</h3><div>In this study, we investigated the changes in brain cortical thickness in patients with facial paralysis following neurorrhaphy treatment at different follow-up times. Using magnetic resonance imaging (MRI) and the CAT12 toolbox, voxel-based whole-brain morphometric (VBM) analysis and region of interest (ROI) of cortical thickness estimation were performed in 11 patients with left facial paralysis before and after hypoglossal-facial nerve neurorrhaphy, and the results were compared to those of 20 healthy controls. All subjects were right-handed and had a left dominant hemisphere. Based on the ROIs, correlation analysis among the cortical structural changes, the House–Brackmann (H-B) grading scale and the compound muscle action potential (cMAP) amplitudes of the facial paralyzed/reinnervated muscles in the patients was conducted.</div></div><div><h3>Results</h3><div>The results show dynamic changes in the thickness in the contralateral right cortex at corresponding functional areas in patients. The thickness of the ROIs was negatively correlated with the duration of facial paralysis from onset to neurorrhaphy but was positively correlated with the improvement in H-B grades and cMAP wave amplitudes recorded in the paralyzed/reinnervated facial muscles of patients. Interestingly, a significant increase in cortical thickness was observed in the ipsilateral left cortex of patients before surgery. However, the increased thickness of the left cortex was then gradually decreased and returned to the reference level of healthy controls following neurorrhaphy and reinnervation of paralyzed facial muscles.</div></div><div><h3>Conclusion</h3><div>We concluded that dynamic changes in both sides of the brain cortex could reflect the state and effect of functional recovery in patients from the onset of facial paralysis before treatment to reinnervation and the return of lost function following neurorrhaphy, suggesting potential observation and treatment targets to predict prognosis and further promote functional recovery.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149437"},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fuzhisan ameliorates cognitive ability in Alzheimer’s disease by p62 and related autophagy regulatory pathways","authors":"Zhaoxu Zhang ,&nbsp;Shuangmei Zhang ,&nbsp;Shen Liu ,&nbsp;Yang He ,&nbsp;Anrong Wang","doi":"10.1016/j.brainres.2024.149436","DOIUrl":"10.1016/j.brainres.2024.149436","url":null,"abstract":"<div><h3>Background</h3><div>Maintaining autophagic homeostasis has been proved to play an important role in Alzheimer’s disease.</div></div><div><h3>Object</h3><div>The aim of this study was to investigate the effect of Fuzhisan(FZS) on autophagic function in Alzheimer’s disease and to elucidate its potential mechanism through the P62 regulatory pathways.</div></div><div><h3>Methods</h3><div>FZS was extracted by water extraction-rotary evaporation method. The novel object recognition test, morris water maze test and Y maze test were used to observe the cognitive and memory ability of APP/PS1 mice. The effects of FZS on the ultrastructure of mice hippocampus were examined by transmission electron microscopy. Molecular level changes were also further detected, including Aβ deposition, tau hyperphosphorylation, SOD, CAT and autophagy related proteins (p62, Nrf2, keap1, mTOR, LC3II/I, Beclin1, Atgs).</div></div><div><h3>Results</h3><div>FZS could alleviate memory and cognitive impairment in APP/PS1 mice, increase the autophagic vesicles and organelle abundance in hippocampus. FZS also reduced the levels of Aβ and tau hyperphosphorylation in the hippocampus of model mice, upregulated the levels of SOD, CAT and autophagy related proteins (Nrf2, LC3II/LC3I, Beclin1, Atg7 and Atg12) as well as downregulated the expression of P62, keap1 and p-mTOR/mTOR proteins. Co-Ip results showed that FZS elevated the levels of p62/LC3 and P62-keap1-Nrf2 complex, but decreased the P62 and keap1 association.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that FZS may affect autophagy function and oxidative stress by regulating P62 and related pathways to promote the clearance of Aβ and phosphorylated tau, thereby improving the cognitive ability of AD, which provided a novel perspective for exploring the potential mechanism of FZS upon AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"Article 149436"},"PeriodicalIF":2.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimethyltryptamine (DMT) and ibogaine elicit membrane effects in HEK cells transiently transfected with the human 5-HT2A receptor","authors":"Jannik Nicklas Eliasen,&nbsp;Uffe Kristiansen,&nbsp;Kristi A. Kohlmeier","doi":"10.1016/j.brainres.2024.149425","DOIUrl":"10.1016/j.brainres.2024.149425","url":null,"abstract":"<div><div>Psychedelics show promise in treating psychiatric disorders. Therapeutic effects appear to involve activation of the 5-Hydroxytryptamine 2A receptor (5-HT_2AR), a G protein-coupled receptor (GPCR). Several SNPs of the 5-HT_2AR naturally occur, which are associated with differences in receptor function and altered responsiveness to treatments. New compounds suspected to act at the 5-HT_2AR are actively being generated. HEK cells are not commonly used to study membrane effects induced by agonists of GPCRs. In this study, for the first time, membrane actions of two psychedelics, dimethyltryptamine (DMT) and ibogaine on HEK cells transiently transfected with either the human wildtype (WT) or the human I197V mutated 5-HT_2AR were investigated using whole-cell electrophysiology. Membrane effects were observed in both genotypes and with both drugs in most cells, while no responses were observed in non-transfected HEK cells suggesting that responses were due to 5-HT_2AR activation. In HEK cells transfected with the I197V SNP, a significantly shorter duration of the DMT response was observed, however there were no differences in drug-elicited amplitudes between drug or receptor genotype. I-V curves showed a significant effect of drug exposure for both DMT and ibogaine at the highest concentration evaluated. Taken together, our data show transfection of the 5-HT_2AR, a GPCR, in HEK cells is able to activate downstream ion channels following exposure to two different 5-HT_2AR agonists. Accordingly, investigations of novel compounds suspected to act at 5-HT_2ARs can include examination of elicitation of ionic currents in 5-HT_2AR transfected HEK cells, and drug effects at SNPs can also be evaluated.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149425"},"PeriodicalIF":2.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}