Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating
| العنوان: | Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating |
|---|---|
| المؤلفون: | Qi Dai, Abdul Rezzak Hamzeh, Marquis P. Vawter, Nayna Sanathara, Lamees Alhassen, Lucas Pauluk, Jasmine Sakr, Amal Alachkar, Xuejie Wang, Ryan F. Yoshimura, Olivier Civelli, Anton Schulmann, Wedad Alhassen |
| المصدر: | International Journal of Neuropsychopharmacology The international journal of neuropsychopharmacology, vol 23, iss 1 |
| بيانات النشر: | Oxford University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Melanin-concentrating hormone, Genome-wide association study, Medical and Health Sciences, Regular Research Articles, chemistry.chemical_compound, Mice, 0302 clinical medicine, Receptors, 80 and over, 2.1 Biological and endogenous factors, Medicine, Pharmacology (medical), Receptors, Somatostatin, Prefrontal cortex, Child, Psychiatry, Aged, 80 and over, Mice, Knockout, Hypothalamic Hormones, Behavior, Animal, AcademicSubjects/SCI01870, Middle Aged, Sensory Gating, Psychiatry and Mental health, Mental Health, medicine.anatomical_structure, Schizophrenia, Child, Preschool, Female, Somatostatin, Adult, AcademicSubjects/MED00415, Adolescent, Knockout, Neuropeptide, Prefrontal Cortex, 03 medical and health sciences, Young Adult, Fetus, Behavioral and Social Science, Genetics, Animals, Humans, Preschool, Aged, Pharmacology, Melanins, Behavior, Memory Disorders, Animal, business.industry, Psychology and Cognitive Sciences, Neurosciences, Infant, medicine.disease, Brain Disorders, Melanin-concentrating hormone receptor, Dorsolateral prefrontal cortex, Disease Models, Animal, Pituitary Hormones, 030104 developmental biology, chemistry, Disease Models, business, Neuroscience, 030217 neurology & neurosurgery, Hormone |
| الوصف: | Background Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone (MCH) system in modulating emotional and cognitive functions. Genome wide association (GWA) studies revealed a potential association between the MCH receptor (MCHR1) gene locus and schizophrenia and the largest GWA study conducted to date shows a credible GWA. Methods We analyze MCHR1 and pro-melanin concentrating hormone (PMCH) RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the MCH system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of MCH expressing neurons using a Cre-inducible diphtheria toxin (iDTR) system. Results MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (FDR p< 0.05, CommonMind and PsychEncode combined datasets, N = 901) while PMCH is below the detection threshold. MCHR1 expression decreased with aging (p = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of PMCH neurons increased repetitive behavior and produced a deficit in sensorimotor gating. Conclusions Our study indicates that early disruption of the MCH system interferes with neurodevelopmental processes which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by MCH may lead to a therapeutic target for early prevention of schizophrenia. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1469-5111 1461-1457 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::061421ef7eb8f896612a43592f139ea3Test http://europepmc.org/articles/PMC7442395Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....061421ef7eb8f896612a43592f139ea3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14695111 14611457 |
|---|