New roles for dopamine D and D receptors in pancreatic beta cell insulin secretion.

Although long-studied in the central nervous system, there is increasing evidence that dopamine (DA) has important roles in the periphery including in metabolic regulation. Insulin-secreting pancreatic β-cells express the machinery for DA synthesis and catabolism, as well as all five DA receptors. In these cells, DA functions as a negative regulator of glucose-stimulated insulin secretion (GSIS), which is mediated by DA D-like receptors including D (D2R) and D (D3R) receptors.

The roles of class I histone deacetylases (HDACs) in memory, learning, and executive cognitive functions: A review.

Coordinated changes in gene expression are critical for synaptic plasticity supporting learning, memory, and optimal cognitive task performance. These gene expression changes are not only mediated by signaling pathways that activate transcription factors, but also by chromatin modifications that influence the accessibility of the transcriptional machinery to specific genomic regions. During the past decade, evidence accumulated that alterations in chromatin-based epigenetic regulation of gene expression are linked to cognitive dysfunctions in the ageing or neurodegenerating brain as well as to cognitive dysfunctions resulting from chronic stress exposure.

Lasting effects of early life stress in mice: interaction of maternal environment and infant genes.

In the mouse, a powerful paradigm of early life stress, infant maternal separation (IMS), can trigger emotional and cognitive dysfunctions in adulthood similar to those found in humans with a history of childhood adversity. The magnitude of IMS effects differs among diverse inbred strains suggesting an interaction between the genetic background of pups and the maternal care they received. Here, we investigated this interaction with studies on reciprocal F1 hybrid mice of the stress-susceptible Balb/c and the resilient C57Bl/6 strains that were either raised by Balb/c mothers (low maternal care) or by C57Bl/6 mothers (higher maternal care) with or without IMS exposure.

Cognitive deficits triggered by early life stress: The role of histone deacetylase 1.

Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive deficits found in neurodegenerative disorders and age-related memory decline. However, the role of HDACs in stress-induced cognitive deficits has not been investigated. In the stress-susceptible mouse strain Balb/c, early life stress triggers a persistent decrease in HDAC expression in the forebrain neocortex, including reduced expression of class I HDACs.

An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine.

Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine.