Strength of cholinergic tone dictates the polarity of dopamine D2 receptor modulation of striatal cholinergic interneuron excitability in DYT1 dystonia.

Strength of cholinergic tone dictates the polarity of dopamine D2 receptor modulation of striatal cholinergic interneuron excitability in DYT1 dystonia. Exp Neurol. 2017 Jun 03;: Authors: Scarduzio M, Zimmerman CN, Jaunarajs KL, Wang Q, Standaert DG, McMahon LL Abstract Balance between cholinergic and dopaminergic signaling is central to striatal control of movement and cognition. In dystonia, a common disorder of movement, anticholinergic therapy is often beneficial. This observation suggests there is a pathological increase in cholinergic tone, yet direct confirmation is lacking. In DYT1, an early-onset genetic form of dystonia caused by a mutation in the protein torsinA (TorA), the suspected heightened cholinergic tone is commonly attributed to faulty dopamine D2 receptor (D2R) signaling where D2R agonists cause excitation of striatal cholinergic interneurons (ChIs), rather than the normal inhibition of firing observed in wild-type animals, an effect known as "paradoxical excitation". Here, we provide for the first time direct measurement of elevated striatal extracellular acetylcholine (ACh) in a knock-in mouse model of human DYT1 dystonia (TorA(∆E/+) mice), confirming a striatal hypercholinergic state. We hypothesized that this elevated extracellular ACh might cause chronic over-activation of muscarinic acetylcholine receptors (mAChRs) and disrupt normal D2R function due to their shared coupling to Gi/o-proteins. We tested this concept i...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

Related Links:

Publication date: Available online 15 October 2019Source: Stem Cell ResearchAuthor(s): Mazid Md Abdul, David P. Ibañez, Ping Zhao, Hao Liu, Xiaofen Zhong, Yingying Li, Meng Zhang, Wenjuan Li, Yunpan Li, Carl Ward, Shuhan Chen, Dongye Wang, Baoming Qin, Miguel A. Esteban, Xiwei Wang, Wenxia Fan, Zhiwei LuoAbstractFamilial Parkinson's disease (PD) can be caused by deleterious mutations in PINK1 (encoding PINK1) in an autosomal recessive manner. Functional studies suggest that PINK1 works as a regulator of mitochondrial homeostasis. However, how loss of PINK1 induces dopaminergic neuron degeneration is still unclear. H...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 15 October 2019Source: Stem Cell ResearchAuthor(s): Meng Zhang, David P. Ibañez, Wenxia Fan, Hao Liu, Xiaofen Zhong, Xiwei Wang, Yingying Li, Mazid Md.Abdul, Wenjuan Li, Yunpan Li, Carl Ward, Shuhan Chen, Dongye Wang, Baoming Qin, Miguel A. Esteban, Ping Zhao, Zhiwei LuoAbstractLoss of function mutations in PARK2 (encoding PARKIN) cause autosomal recessive Parkinson's disease (PD), which often manifests at a juvenile age. Molecular and biochemical studies show that PARKIN functions as an E3 ubiquitin ligase controlling mitochondrial homeostasis. Yet, the exact mechanisms are unclea...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: 15 October 2019Source: Cell Reports, Volume 29, Issue 3Author(s): Sebastian Lobentanzer, Geula Hanin, Jochen Klein, Hermona SoreqSummaryRNA sequencing analyses are often limited to identifying lowest p value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large-scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA sequencing of human male- and female-originating cell lines, and connectomics of transcription factor and microRNA interactions with perturbed...
Source: Cell Reports - Category: Cytology Source Type: research
Authors: Yang M, Yang C, Liu T, London ED Abstract Objectives: Despite the prevalence of methamphetamine-associated psychosis, how characteristics of drug use affect the severity and clinical course, and its optimal treatments have not been established. We addressed these questions, assessing clinical features of methamphetamine-associated psychosis, and compared it with primary psychosis. Methods: Hospitalised patients with methamphetamine-associated (n = 70) or primary schizophrenic psychosis (n = 70) were matched on sex, age and duration of psychosis. Association of drug use variables...
Source: International Journal of Psychiatry in Clinical Practice - Category: Psychiatry Tags: Int J Psychiatry Clin Pract Source Type: research
Publication date: Available online 15 October 2019Source: Life SciencesAuthor(s): He Li, Yin Luo, Luojiang Zhu, Weilong Hua, Yongxin Zhang, Hongjian Zhang, Lei Zhang, Zifu Li, Pengfei Xing, Yongwei Zhang, Bo Hong, Pengfei Yang, Jianmin LiuAbstractGlia is an important component of the nervous system that is involved in neurotransmitter uptake, signal transduction, myelin synthesis, neurodevelopment, and immune response. Exosomes are extracellular vesicles that are secreted from certain types of cells, and are known to mediate glia function. Glia-derived exosomes (GDEs) can transport proteins, nucleotides and cellular waste,...
Source: Life Sciences - Category: Biology Source Type: research
BACKGROUND: Identifying neuropsychiatric disorders is essential for prompt treatment to reduce morbidity. Among these disorders, anxiety and depression have been frequently associated with Parkinson disease (PD), particularly among elderly population. ...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
ConclusionCondom catheter is frequently used to manage male urinary incontinence but it should not be used carelessly or overlooked as it can cause severe complications such as penile strangulation and penile gangrene.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
CONCLUSION: DO is almost universal in all patients with PD complaining of OAB symptoms (97.1%). However, a significant percentage of patients also had BOO (36.8%), DU (47%), and increased PVR (16.7%) indicating that neurogenic DO may not be the only cause of OAB symptoms in PD patients. PMID: 31607100 [PubMed]
Source: International Neurourology Journal - Category: Urology & Nephrology Tags: Int Neurourol J Source Type: research
Harvard University scientists discovered 10 genes that, when disrupted, raise schizophrenia risks. Two of them are involved in brain cell communication and may be good drug targets.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
CONCLUSIONS: For most mental disorders, refugees were less likely to be admitted to hospital for suicide attempt or die by suicide compared with Swedish-born individuals. Further research on risk and protective factors for suicide attempt and suicide among refugees with mental disorders is warranted. DECLARATION OF INTEREST: None. PMID: 31608856 [PubMed - as supplied by publisher]
Source: The British Journal of Psychiatry for Mental Science - Category: Psychiatry Tags: Br J Psychiatry Source Type: research
More News: Brain | Dyskinesia | Dystonia | Genetics | Huntington's Disease | Neurology | Parkinson's Disease | Schizophrenia