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Catecholamines such as noradrenaline and adrenaline have been implicated in numerous physiological processes but, although catecholamine synthesis begins at mid-gestation, previous studies have provided little evidence for any role in early development. Furthermore, there are several case reports of humans with noradrenaline deficiency. To investigate this,(More)
Hematopoietic stem and progenitor cells (HSPC), attracted by the chemokine CXCL12, reside in specific niches in the bone marrow (BM). HSPC migration out of the BM is a critical process that underlies modern clinical stem cell transplantation. Here we demonstrate that enforced HSPC egress from BM niches depends critically on the nervous system. UDP-galactose(More)
The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca(2+)-stimulated adenylyl cyclase activity was reduced 40-60% in the hippocampus, neocortex, and cerebellum. Long-term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative(More)
Mice with a targeted disruption of the dopamine beta-hydroxylase (DBH) gene are unable to synthesize norepinephrine (NE) and epinephrine. These mice have elevated levels of dopamine in most tissues, although the levels are only a fraction of those normally found for NE. It is noteworthy that NE can be restored to normal levels in many tissues after a single(More)
A role for norepinephrine in learning and memory has been elusive and controversial. A longstanding hypothesis states that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. We tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine, as well as control(More)
The roles of norepinephrine (NE) and epinephrine in behavior were investigated by targeted disruption of the dopamine beta-hydroxylase (Dbh) gene, thereby eliminating these compounds in vivo. Most heterozygous pups born to Dbh-/- females died within several days of birth and were often found scattered within the bedding. Potential causes including deficits(More)
Exogenous leptin enhances energy utilization in ob/ob mice by binding its hypothalamic receptor and selectively increasing peripheral fat oxidation. Leptin also increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but the neurotransmitter that mediates this effect has not been established. The present experiments sought to(More)
Aberrant aggregation of alpha-synuclein (alpha-syn) to form fibrils and insoluble aggregates has been implicated in the pathogenic processes of many neurodegenerative diseases. Despite the dramatic effects of dopamine in inhibiting the formation of alpha-syn fibrils by stabilization of oligomeric intermediates in cell-free systems, no studies have examined(More)
Mice unable to synthesize norepinephrine (NE) were created by targeted disruption of the dopamine beta-hydroxylase (DBH) gene. DBH-deficient (DBH -/-) mice display normal home cage activity; however, they swim more slowly than their littermates, and some drown. The mutant mice also perform less well on a rapidly rotating rod, and approximately 20% do not(More)
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)α signalling in vitro can prevent both intracellular and extracellular Aβ accumulation. RARα signalling increases the expression of a disintegrin and metalloprotease 10, an α-secretase(More)