Confirmation of Decreased Rates of Cerebral Protein Synthesis in a Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results in intellectual disability and, in ∼50% of patients, autism spectrum disorder. The protein products that are altered in TSC (TSC1 and TSC2) form a complex to inhibit the mammalian target of rapamycin [mTOR; mTOR complex 1 (mTORC1)] pathway. This pathway has been shown to affect the process of mRNA translation through its action on ribosomal protein S6 and 4-elongation binding protein 1.

Effects of Treatment With Hypnotics on Reduced Sleep Duration and Behavior Abnormalities in a Mouse Model of Fragile X Syndrome.

Many patients with fragile X syndrome (FXS) have sleep disturbances, and knockout (KO) mice (a model of FXS) have reduced sleep duration compared to wild type (WT). Sleep is important for brain development, and chronic sleep restriction during development has long-lasting behavioral effects in WT mice. We hypothesized that the sleep abnormalities in FXS may contribute to behavioral impairments and that increasing sleep duration might improve behavior.

Effects of chronic inhibition of phosphodiesterase-4D on behavior and regional rates of cerebral protein synthesis in a mouse model of fragile X syndrome.

Fragile X Syndrome (FXS) is caused by silencing the FMR1 gene which results in intellectual disability, hyperactivity, sensory hypersensitivity, autistic-like behavior, and susceptibility to seizures. This X-linked disorder is also associated with reduced cAMP levels in humans as well as animal models. We assessed the therapeutic and neurochemical effects of chronic administration of the phosphodiesterase-4D negative allosteric modulator, BPN14770, in a mouse model of FXS (Fmr1 KO).

Behavior Testing in Rodents: Highlighting Potential Confounds Affecting Variability and Reproducibility.

Rodent models of brain disorders including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases are essential for increasing our understanding of underlying pathology and for preclinical testing of potential treatments. Some of the most important outcome measures in such studies are behavioral. Unfortunately, reports from different labs are often conflicting, and preclinical studies in rodent models are not often corroborated in human trials.

Sleep Duration in Mouse Models of Neurodevelopmental Disorders.

Sleep abnormalities are common in patients with neurodevelopmental disorders, and it is thought that deficits in sleep may contribute to the unfolding of symptoms in these disorders. Appreciating sleep abnormalities in neurodevelopmental disorders could be important for designing a treatment for these disorders. We studied sleep duration in three mouse models by means of home-cage monitoring: (tuberous sclerosis complex), oxytocin receptor () knockout (KO) (autism spectrum disorders), and KO (Phelan-McDermid syndrome).

Increased rates of cerebral protein synthesis in Shank3 knockout mice: Implications for a link between synaptic protein deficit and dysregulated protein synthesis in autism spectrum disorder/intellectual disability.

SHANK3 is a postsynaptic scaffolding protein that plays a critical role in synaptic development and brain function. Mutations in SHANK3 are implicated in Phelan-McDermid syndrome (PMS), a neurodevelopmental disorder characterized by autistic-like behavior, delayed speech, hypotonia, and intellectual disability (ID). Moreover, mutations in SHANK3 occur in 1-2% of cases of idiopathic autism spectrum disorder (ASD).

Association Between Sleep Deficiencies with Behavioral Problems in Autism Spectrum Disorder: Subtle Sex Differences.

Sleep problems are prevalent in people with autism spectrum disorder (ASD). Several studies have shown an association between sleep problems and severity of ASD-related behaviors. Most of these studies have not addressed potential sex differences either in the prevalence of the sleep problems or in their association with the manifestation of other behavioral issues in ASD.

Sex-Selective Effects on Behavior in a Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that is caused by a mutation in either or TSC affects multiple systems of the body, and patients with TSC display a range of neurologic and behavioral manifestations including seizures, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and mood disorders. Whereas behavioral phenotypes of many mouse models have been studied, the effects of sex have, for the most part, not been explored. We studied adult male and female heterozygous and control mice to investigate the influence of sex and genotype on behavior.

Chronic Sleep Restriction in Developing Male Mice Results in Long Lasting Behavior Impairments.

Sleep abnormalities are prevalent in autism spectrum disorders (ASD). Moreover, the severity of ASD symptoms are correlated with the degree of disturbed sleep. We asked if disturbed sleep during brain development itself could lead to ASD-like symptoms, particularly behavioral manifestations.

Comparative Behavioral Phenotypes of KO, Het, and KO/ Het Mice.

Fragile X syndrome (FXS) is caused by silencing of the gene leading to loss of the protein product fragile X mental retardation protein (FMRP). FXS is the most common monogenic cause of intellectual disability. There are two known mammalian paralogs of FMRP, FXR1P, and FXR2P.

Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD). It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the gene. This is modeled in the mouse by deletion of ( KO).

Decreased rates of cerebral protein synthesis measured in vivo in a mouse model of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder affecting about 1 in 6000 people and is caused by mutations in either TSC1 or TSC2. This disorder is characterized by increased activity of mammalian target of rapamycin complex 1 (mTORC1), which is involved in regulating ribosomal biogenesis and translation initiation. We measured the effects of Tsc2 haploinsufficiency (Tsc2 ) in 3-month-old male mice on regional rates of cerebral protein synthesis (rCPS) by means of the in vivo L-[1- C]leucine method.