التفاصيل البيبلوغرافية
| العنوان: |
Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain |
| المؤلفون: |
Fu, Su, Sun, Haojie, Wang, Jiaxin, Gao, Shuaixin, Zhu, Liu, Cui, Kun, Liu, Shimeng, Qi, Xuetao, Guan, Rui, Fan, Xiaocen, Liu, Qingying, Chen, Wen, Su, Li, Cui, Shuang, Liao, Feifei, Liu, Fengyu, Wong, Catherine CL, Yi, Ming, Wan, You |
| المصدر: |
Autophagy (2024) (In press). |
| بيانات النشر: |
Landes Bioscience |
| سنة النشر: |
2024 |
| المجموعة: |
University College London: UCL Discovery |
| مصطلحات موضوعية: |
Autophagy, Cell Biology, chronic neuropathic pain, comorbid anxiety, CONNECTIVITY, DISORDERS, HIPPOCAMPUS, Life Sciences & Biomedicine, MECHANISMS, MEDIAL PREFRONTAL CORTEX, MODEL, NEURODEGENERATION, neuronal ensemble, NEUROSTEROIDS, prelimbic cortex, Science & Technology, synaptic homeostasis, THALAMUS |
| الوصف: |
A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL. Chemogenetic inactivation of this comorbid anxiety-related neuronal ensemble relieved pain-induced anxiety-like behaviors. Rescuing macroautophagy impairment in this neuronal ensemble relieved chronic pain-associated anxiety and mechanical allodynia and restored synaptic homeostasis at the molecular level. By contrast, artificial disruption of macroautophagy induced early-onset co-morbid anxiety in neuropathic rats, but not general anxiety in normal rats. Taken together, our work identifies causal linkage between PrL neuronal macroautophagy dysfunction and comorbid anxiety in neuropathic pain and provides novel insights into the role of PrL by differentiating its contribution in pain-induced comorbid anxiety from its modulation over general anxiety-like behaviors. Abbreviation: AAV: adeno-associated viruses; ACC: anterior cingulate cortex; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; CAMK2/CaMKII: calcium/calmodulin-dependent protein kinase II; CNO: clozapine-N-oxide; CQ: chloroquine; DIA: data independent acquisition; DIO: double floxed inverse orf; DLG4/PSD-95: discs large MAGUK scaffold protein 4; Dox: doxycycline; GABA: γ-aminobutyric acid; GFP: green fluorescent protein; GO: gene ontology; Gi: inhibitory guanine nucleotide-binding proteins; HsCHRM4/M4D: human cholinergic receptor muscarinic 4; HsSYN: human synapsin; KEGG: Kyoto encyclopedia of genes and genomes; LAMP1: lysosomal-associated membrane protein 1; LC3-II: PE ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10193546/ |
| الاتاحة: |
https://discovery.ucl.ac.uk/id/eprint/10193546/ |
| رقم الانضمام: |
edsbas.1E00B4B |
| قاعدة البيانات: |
BASE |