Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits
Abstract Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-cho...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01890-0 |
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| author | Xiaotian Qu Pingyuan Yang Rongwei Zhai Zhi-Qi Xiong |
| author_facet | Xiaotian Qu Pingyuan Yang Rongwei Zhai Zhi-Qi Xiong |
| author_sort | Xiaotian Qu |
| collection | DOAJ |
| description | Abstract Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure. Our results indicate that METH exposure disrupts RtTg neurons at the transcriptional level and results in an increased activation ratio of RtTg under 5-CSRTT conditions. Crucially, chemogenetic inactivation of these neurons or RtTg lesion attenuated METH-induced attention deficits, whereas their activation reproduced the deficits. These findings underscore the critical role of RtTg neurons in mediating METH-induced attention deficits, positioning RtTg as a promising therapeutic target for the treatment of attention deficits linked to chronic METH use. |
| format | Article |
| id | doaj-art-b3edd3bde2e5486ab1a73ce9b083ff85 |
| institution | OA Journals |
| issn | 2051-5960 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-b3edd3bde2e5486ab1a73ce9b083ff852025-08-20T02:33:32ZengBMCActa Neuropathologica Communications2051-59602024-11-0112111510.1186/s40478-024-01890-0Inhibition of RtTg neurons reverses methamphetamine-induced attention deficitsXiaotian Qu0Pingyuan Yang1Rongwei Zhai2Zhi-Qi Xiong3Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineLin Gang LaboratoryInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence TechnologyAbstract Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure. Our results indicate that METH exposure disrupts RtTg neurons at the transcriptional level and results in an increased activation ratio of RtTg under 5-CSRTT conditions. Crucially, chemogenetic inactivation of these neurons or RtTg lesion attenuated METH-induced attention deficits, whereas their activation reproduced the deficits. These findings underscore the critical role of RtTg neurons in mediating METH-induced attention deficits, positioning RtTg as a promising therapeutic target for the treatment of attention deficits linked to chronic METH use.https://doi.org/10.1186/s40478-024-01890-0Methamphetamine (METH)AttentionSingle-nuclei RNA sequencing (snRNA-seq)Reticulotegmental nucleus (RtTg)Five-choice serial reaction time task (5-CSRTT)Designer receptors exclusively activated by designer drugs (DREADD) |
| spellingShingle | Xiaotian Qu Pingyuan Yang Rongwei Zhai Zhi-Qi Xiong Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits Acta Neuropathologica Communications Methamphetamine (METH) Attention Single-nuclei RNA sequencing (snRNA-seq) Reticulotegmental nucleus (RtTg) Five-choice serial reaction time task (5-CSRTT) Designer receptors exclusively activated by designer drugs (DREADD) |
| title | Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits |
| title_full | Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits |
| title_fullStr | Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits |
| title_full_unstemmed | Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits |
| title_short | Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits |
| title_sort | inhibition of rttg neurons reverses methamphetamine induced attention deficits |
| topic | Methamphetamine (METH) Attention Single-nuclei RNA sequencing (snRNA-seq) Reticulotegmental nucleus (RtTg) Five-choice serial reaction time task (5-CSRTT) Designer receptors exclusively activated by designer drugs (DREADD) |
| url | https://doi.org/10.1186/s40478-024-01890-0 |
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