Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson's Disease.
10.1007/s12264-024-01320-0
- Author:
Han-Ting XU
1
;
Xiao-Ya XI
1
;
Shuang ZHOU
1
;
Yun-Yong XIE
1
;
Zhi-San CUI
1
;
Bei-Bei ZHANG
1
;
Shu-Tao XIE
1
;
Hong-Zhao LI
1
;
Qi-Peng ZHANG
1
;
Yang PAN
2
;
Xiao-Yang ZHANG
3
;
Jing-Ning ZHU
4
Author Information
1. State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Anesthesiology, Nanjing Drum Tower Hospital, and Department of Physiology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
2. Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China. panyang@njmu.edu.cn.
3. State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Anesthesiology, Nanjing Drum Tower Hospital, and Department of Physiology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. xiaoyangzhang@nju.edu.cn.
4. State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Anesthesiology, Nanjing Drum Tower Hospital, and Department of Physiology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. jnzhu@nju.edu.cn.
- Publication Type:Journal Article
- Keywords:
H1 receptor;
H2 receptor;
Histamine;
Parkinson’s disease;
Ventral anterior nucleus of the thalamus
- MeSH:
Animals;
Histamine/metabolism*;
Male;
Oxidopamine/toxicity*;
Rats;
Ventral Thalamic Nuclei/physiopathology*;
Rats, Sprague-Dawley;
Disease Models, Animal;
Parkinson Disease/metabolism*;
Neurons/physiology*;
Humans;
Optogenetics
- From:
Neuroscience Bulletin
2025;41(4):551-568
- CountryChina
- Language:English
-
Abstract:
The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K+ channels, or Ca2+-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
