New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity.

Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases.

Hypocretin/orexin deficiency decreases cocaine abuse liability.

Compelling evidence indicates that hypocretin/orexin signaling regulates arousal, stress and reward-seeking behaviors. However, most studies on drug reward-related processes have so far described the effects of pharmacological blockers disrupting hypocretin/orexin transmission. We report here an extensive study on cocaine-related behaviors in hypocretin/orexin-deficient mice (KO) and their heterozygous (HET) and wildtype (WT) littermates.

Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression.

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity.

Controversies about a common etiology for eating and mood disorders.

Obesity and depression represent a growing health concern worldwide. For many years, basic science and medicine have considered obesity as a metabolic illness, while depression was classified a psychiatric disorder. Despite accumulating evidence suggesting that obesity and depression may share commonalities, the causal link between eating and mood disorders remains to be fully understood.

Evidence for a compulsive-like behavior in rats exposed to alternate access to highly preferred palatable food.

Converging evidence suggests that recurrent excessive calorie restriction causes binge eating by promoting behavioral disinhibition and overeating. This interpretation suggests that cognitive adaptations may surpass physiological regulations of metabolic needs after recurrent cycles of dieting and binging. Intermittent access to palatable food has long been studied in rats, but the consequences of such diet cycling procedures on the cognitive control of food seeking remain unclear.

Deletion of CREB-regulated transcription coactivator 1 induces pathological aggression, depression-related behaviors, and neuroplasticity genes dysregulation in mice.

Background: Mood disorders are polygenic disorders in which the alteration of several susceptibility genes results in dysfunctional mood regulation. However, the molecular mechanisms underlying their transcriptional dysregulation are still unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) have been implicated in rodent models of depression.

A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus.

The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM.

Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning.

Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure of the immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM.