ArticleEuropean neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology2014
Dysregulated intracellular signaling in the striatum in a pathophysiologically grounded model of Tourette syndrome.
Article in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
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- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
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- Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits.Translational psychiatry · 2023Article
- Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathwayPharmaceutical biology · 2022Article
- Striatal Syntaxin 1A Is Associated with Development of Tourette Syndrome in an Iminodipropionitrile-Induced Animal Model.Disease markers · 2022Article
- Animal Models for OCD Research.Current topics in behavioral neurosciences · 2021Review
- Modulation of dopamine DeLife · 2020Article
- The histidine decarboxylase model of tic pathophysiology: a new focus on the histamine HBritish journal of pharmacology · 2020Review
- Ningdong Granule Upregulates the Striatal DA Transporter and Attenuates Stereotyped Behavior of Tourette Syndrome in Rats.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology.Neuroscience · 2018Article
- The PNKD gene is associated with Tourette Disorder or Tic disorder in a multiplex family.Molecular psychiatry · 2018Article
- Modeling tics in rodents: Conceptual challenges and paths forward.Journal of neuroscience methods · 2017Review
- Targeted Interneuron Depletion in the Dorsal Striatum Produces Autism-like Behavioral Abnormalities in Male but Not Female Mice.Biological psychiatry · 2017Article
- Histamine modulation of the basal ganglia circuitry in the development of pathological grooming.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders.Translational psychiatry · 2017Article
- Histidine Decarboxylase Knockout Mice as a Model of the Pathophysiology of Tourette Syndrome and Related Conditions.Handbook of experimental pharmacology · 2017Review
- Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation.Brain, behavior, and immunity · 2016Article
- The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Tic disorders produce substantial morbidity, but their pathophysiology remains poorly understood. Convergent evidence suggests that dysregulation of the cortico-basal ganglia circuitry is central to the pathogenesis of tics. Tourette syndrome (TS), the most severe end of the continuum of tic disorders, is substantially genetic, but causative mutations have been elusive. We recently described a mouse model, the histidine decarboxylase (Hdc) knockout mouse, that recapitulates a rare, highly penetrant mutation found in a single family; these mice exhibit TS-like phenomenology. These animals have a global deficit in brain histamine and a consequent dysregulation of DA in the basal ganglia. Histamine modulation of DA effects is increasingly appreciated, but the mechanisms underlying this modulation remain unclear; the consequences of modest DA elevation in the context of profound HA deficiency are difficult to predict, but understanding them in the Hdc knockout mouse may provide generalizable insights into the pathophysiology of TS. Here we characterized signaling pathways in striatal cells in this model system, at baseline and after amphetamine challenge. In vivo microdialysis confirms elevated DA in Hdc-KO mice. We find dephosphorylation of Akt and its target GSK3β and activation of the MAPK signaling cascade and its target rpS6; these are characteristic of the effects of DA on D2- and D1-expressing striatal neurons, respectively. Strikingly, there is no alteration in mTOR signaling, which can be regulated by DA in both cell types. These cellular effects help elucidate striatal signaling abnormalities in a uniquely validated mouse model of TS and move towards the identification of new potential therapeutic targets for tic disorders.
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