Mice Lacking the Circadian Modulators SHARP1 and SHARP2 Display Altered Sleep and Mixed State Endophenotypes of Psychiatric Disorders

Autor: Sven P. Wichert, Lisa Reinecke, Moritz J. Rossner, Christina Kroos, Reshma Taneja, Michael C. Wehr, Ali Shahmoradi, Henrik Oster, Magdalena M. Brzózka, Paul Christian Baier, Johannes Hirrlinger
Rok vydání: 2014
Předmět:
Male
Gene Expression
lcsh:Medicine
Anxiety
Biochemistry
Behavioral Neuroscience
Basic Helix-Loop-Helix Transcription Factors
Medicine and Health Sciences
Gene Regulatory Networks
lcsh:Science
Clozapine
Neuroscience of sleep
Prepulse inhibition
Neuronal Plasticity
Multidisciplinary
Prepulse Inhibition
Mental Disorders
Sleep in non-human animals
Circadian Rhythm
CLOCK
Circadian Rhythms
Neurology
Schizophrenia
Research Article
PER1
medicine.medical_specialty
Endophenotypes
Biology
DNA-binding proteins
Genetics
medicine
Animals
Gene Regulation
Circadian rhythm
Wakefulness
Psychiatry
Anaysis of variance
Animal behavior
Circadian oscillators
Circadian rhythms
Electroencephalography
Gene expression
Mice
Sleep
Biology and life sciences
Gene Expression Profiling
lcsh:R
Proteins
Computational Biology
medicine.disease
Mice
Inbred C57BL
Repressor Proteins
Gene Expression Regulation
Cellular Neuroscience
Endophenotype
Exploratory Behavior
Sleep Deprivation
lcsh:Q
Gene Function
Sleep Disorders
Chronobiology
Transcription Factors
Neuroscience
Zdroj: PLoS ONE, Vol 9, Iss 10, p e110310 (2014)
PLoS One
PLoS ONE
ISSN: 1932-6203
Popis: Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2. peerReviewed
Databáze: OpenAIRE
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