NEUROENDOCRINOLOGY
·
2024
·
IF 3.2
Zhang Jiaxian,Lai Wanlin,Tang Yusha,Gao Jing,Zhou Xiangyang,Chen Lei
Introduction:
In women of childbearing age with epilepsy, 40% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy. Methods:
A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. Susceptibility was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35. Results:
This study revealed that letrozole induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with anti-epileptic status in PCOS rats. Conclusion:
This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS
研究领域:
神经科学
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内分泌学
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癫痫研究
·
生殖医学
✓ 已验证
DOI
PubMed
高影响因子
EMBO REPORTS
·
2023
·
IF 7.7
Zhi-Jun Zhang,Han-Yu Shao,Chuan Liu,Hao-Lin Song,Xiao-Bo Wu,De-Li Cao,Meixuan Zhu,Yuan-Yuan Fu,Juan Wang,Yong-Jing Gao
A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11-SDH) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1+) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor-expressing (GRPR+) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch.
研究领域:
神经科学
·
药理学
·
疼痛研究
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2023
·Vol. 18
·期 10
·2315
·
IF 6.1
Duan Tian-Qi,Gao Zhao-Lin,Luo Ai-Xiang,Chen Dan,Tong Jian-Bin,Huang Ju-Fang
Adipose mesenchymal stem cells (ADSCs) have protective effects against glutamate -induced excitotoxicity , but ADSCs are limited in use for treatment of optic nerve injury. Studies have shown that the extracellular vesicles (EVs) secreted by ADSCs (ADSC-EVs) not only have the function of ADSCs, but also have unique advantages including non-immunogenicity, low probability of abnormal growth, and easy access to target cells. In the present study, we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate -induced damage to retinal morphology and electroretinography . In addition, R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate -induced overload of intracellular calcium, downregulation of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPAR) subunit GluA2 , and phosphorylation of GluA2 and protein kinase C alpha in vitro . A protein kinase C alpha agonist, 12-O-tetradecanoylphorbol 13-acetate, inhibited the neuroprotective effects of ADSC-EVs on glutamate -induced R28 cells . These findings suggest that ADSC-EVs ameliorate glutamate -induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.
研究领域:
神经科学
·
细胞生物学
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眼科学
·
干细胞研究
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产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
·
IF 5.168
Qin Yang,Yi-Da Hu,Xue-Feng Wang,Fang-Shuo Zheng
Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro , NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy.
研究领域:
神经科学
·
药理学
·
电生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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