Transglutaminase 2 Induces Deficits in Social Behavior in Mice.

Impairments in social behavior are highly implicated in many neuropsychiatric disorders. Recent studies indicate a role for endoplasmic reticulum (ER) stress in altering social behavior, but the underlying mechanism is not known. In the present study, we examined the role of transglutaminase 2 (TG2), a calcium-dependent enzyme known to be induced following ER stress, in social behavior in mice.

Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior.

Major depressive disorder (MDD) is one of the most common and debilitating neuropsychiatric illnesses. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of MDD. The complement system represents one of the major effector mechanisms of the innate immune system, and plays a critical role in inflammation.

Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors.

Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder.

The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress.

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens.

Estrogen Signaling as a Therapeutic Target in Neurodevelopmental Disorders.

Estrogens, the primary female sex hormones, were originally characterized through their important role in sexual maturation and reproduction. However, recent studies have shown that estrogens play critical roles in a number of brain functions, including cognition, learning and memory, neurodevelopment, and adult neuroplasticity. A number of studies from both clinical as well as preclinical research suggest a protective role of estrogen in neurodevelopmental disorders including autism spectrum disorder (ASD) and schizophrenia.

The Neurobiological Basis for Social Affiliation in Autism Spectrum Disorder and Schizophrenia.

Social interaction and communication are complex behavioral paradigms involving many components. Many different neurotransmitters, hormones, sensory inputs, and brain regions are involved in the act of social engagement and verbal or nonverbal communication. Autism Spectrum Disorder (ASD) and schizophrenia are two neurodevelopmental disorders that have social and language deficits as hallmark symptoms, but show very different etiologies.

Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects.

Although stress has been implicated in the pathophysiology of autistic spectrum disorder (ASD), it is not known whether glucocorticoid receptor (GR) levels are altered in the brain of subjects with ASD. The messenger RNA (mRNA) levels of GR isoforms (GRα, GRβ, GRγ, and GRP), mineralocorticoid receptor (MR), GR co-chaperones (FKBP5, PTGES3, and BAG1), and inflammatory cytokines (IL-6, IL-1β, and IFN-γ) were examined in the postmortem middle frontal gyrus tissues of 13 ASD and 13 age-matched controls by qRT-PCR. The protein levels were examined by Western blotting.

Ubiquitin-proteasome dependent degradation of GABAAα1 in autism spectrum disorder.

Background: Although the neurobiological basis of autism spectrum disorder (ASD) is not fully understood, recent studies have indicated the potential role of GABAA receptors in the pathophysiology of ASD. GABAA receptors play a crucial role in various neurodevelopmental processes and adult neuroplasticity. However, the mechanism(s) of regulation of GABAA receptors in ASD remains poorly understood.

Dysregulation of estrogen receptor beta (ERβ), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects.

Background: Autism spectrum disorders (ASD) are much more common in males than in females. Molecular alterations within the estrogen receptor (ER) signaling pathway may contribute to the sex difference in ASD, but the extent of such abnormalities in the brain is not known.

Methods: Postmortem middle frontal gyrus tissues (13 ASD and 13 control subjects) were used.

Glucocorticoid regulates parkin expression in mouse frontal cortex: implications in schizophrenia.

Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of various psychiatric illnesses including schizophrenia and depression. Studies in rodents have reported dose and time dependent effects of glucocorticoids on the expression of proteins related to neuroplasticity. However, the mechanism(s) involved in the regulation of proteins by glucocorticoids are not clear.