The CRF System as a Therapeutic Target for Neuropsychiatric Disorders.

The major neuropsychiatric disorders are devastating illnesses that are only modestly responsive to treatment. Improving the treatment of these conditions will require innovative new strategies that depart from previously focused-on pharmacological mechanisms. Considerable preclinical and clinical data indicate corticotropin-releasing factor (CRF) signaling as a target for new psychotropic drug development.

Chronic fluoxetine dissociates contextual from auditory fear memory.

Fluoxetine is a medication used to treat Major Depressive Disorder and other psychiatric conditions. These experiments studied the effects of chronic fluoxetine treatment on the contextual versus auditory fear memory of mice. We found that chronic fluoxetine treatment of adult mice impaired their contextual fear memory, but spared auditory fear memory.

Trauma exposure and PTSD symptoms associate with violence in inner city civilians.

Understanding whether a history of psychological trauma is associated with perpetrating aggressive and violent behavior is of critical importance to public health. This relationship is especially important to study within urban areas where violence is prevalent. In this paper we examined whether a history of trauma or Post Traumatic Stress Disorder (PTSD) in inner city civilians was associated with violent behavior.

Data on Arc and Zif268 expression in the brain of the α-2A adrenergic receptor knockout mouse.

The α2-adrenergic receptor (α2-AR) is widely distributed in the brain with distinct roles for α2-AR subtypes (A, B and C). In this article, data are provided on Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 expression in the brain of the α2A-AR knockout (α2A-AR KO) mouse. These data are supplemental to an original research article examining Arc and Zif268 expression in rats injected with the α2-AR antagonist, RX821002 (http://dx.

Developmental DSP4 effects on cortical Arc expression.

Activity Regulated Cytoskeleton Associated Protein (Arc) is an immediate early gene that is critical to brain plasticity. In this study, norepinephrine's regulation of Arc expression was examined during different stages of postnatal development. Rats were injected with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a selective noradrenergic neurotoxin, during preadolescence (PND 0 or 13), adolescence (PND 23 or 48) or adulthood (PND 60).

Interdependent adrenergic receptor regulation of Arc and Zif268 mRNA in cerebral cortex.

Norepinephrine is a neurotransmitter that signals by stimulating the α1, α2 and β adrenergic receptor (AR). We determined the role of these receptors in regulating the immediate early genes, Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 in the rat cerebral cortex. RX821002, an α2-AR antagonist, produced Arc and Zif268 elevations across cortical layers.

Empathic fear responses in mice are triggered by recognition of a shared experience.

Empathy is an important psychological capacity that involves the ability to recognize and share emotions with others. In humans, empathy for others is facilitated by having had a similar prior experience. It increases with the intensity of distress that observers believe is occurring to others, and is associated with acute emotional responses to witnessing others' distress.

Elimination of dendritic spines with long-term memory is specific to active circuits.

Structural changes in brain circuits active during learning are thought to be important for long-term memory storage. If these changes support long-term information storage, they might be expected to be present at distant time points after learning, as well as to be specific to the circuit activated with learning, and sensitive to the contingencies of the behavioral paradigm. Here, we show such changes in the hippocampus as a result of contextual fear conditioning.

Exploration of bovine milk proteome in colostral and mature whey using an ion-exchange approach.

In addition to milk's nutritional role, it contains immunoglobulins (antibodies) and immunoregulatory proteins that are active in the digestive tract of newborns. However, knowledge of the repertoire of milk proteins remains meager. In this work, we report an ion-exchange-based protein fractionation method that allows in-depth exploration of the whey proteome in bovine milk; 293 unique gene products were identified, of which 176 were newly identified in whey.

Comparison of the maturation of the adrenergic and serotonergic neurotransmitter systems in the brain: implications for differential drug effects on juveniles and adults.

Our understanding of the development of neurotransmitter systems in the central nervous system has increased greatly over the past three decades and it has become apparent that drug effects on the developing nervous system may differ considerably from effects on the mature nervous system. Recently it has become clear there are significant differences in the effectiveness of antidepressant drug classes in children and adolescents compared to adults. Whereas the selective serotonin reuptake inhibitors are effective in treating all ages from children to adults, the tricyclic antidepressants, many of which inhibit norepinephrine reuptake, have been shown to be ineffective in treating children and adolescents even though they are effective in adults.

Clinical experience with an integrated continuous glucose sensor/insulin pump platform: a feasibility study.

The recent US Food and Drug Administration approval of an integrated real-time continuous glucose monitoring (CGM) system and insulin pump (Medtronic Mini-Med Paradigm REAL-Time System; Medtronic MiniMed, Inc., Northridge, Calif) is the most recent breakthrough paving the way toward the development of a closedloop insulin delivery system that could revolutionize diabetes care. An early prototype of the MiniMed Paradigm REAL-Time System--which provided both realtime CGM and insulin pump therapy but was not yet fully integrated--was tested in 20 volunteer subjects with type 1 diabetes who wore the device for up to 2 y.

Analysis of brain adrenergic receptors in dopamine-beta-hydroxylase knockout mice.

The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-beta-hydroxylase (DBH). Mice with a homozygous deletion of DBH (Dbh-/-) have a selective and complete absence of norepinephrine. The purpose of this study was to assess the expression of alpha-1, alpha-2 and beta adrenergic receptors (alpha1-AR, alpha2-AR and beta-AR) in the postnatal absence of norepinephrine by comparing noradrenergic receptors in Dbh-/- mice with those in Dbh heterozygotes (Dbh+/-), which have normal levels of norepinephrine throughout life.

A transient expression of functional alpha2-adrenergic receptors in white matter of the developing brain.

Norepinephrine is a neurotransmitter with peripheral and central actions mediated by alpha-1, alpha-2, and beta-adrenergic receptors. In this paper, we report an expression of alpha-2 adrenergic receptors in developing white matter tracts as revealed by [(3)H]RX821002 autoradiography. In rats, these receptors are present in the corpus callosum and anterior commissure at gestational day 20.