A vitamin for the brain

Shearer, Kirsty; Stoney, Patrick N.; Morgan, Peter J.; McCaffery, Peter

doi:10.1016/j.tins.2012.08.005

Cited by 125 publications

(126 citation statements)

References 110 publications

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“…Thus, Dock4 may exert diverse functional roles in multiple neuronal developmental stages, such as neuronal migration, synapse formation, and plasticity. Notably, emerging evidence reveals that RA signaling is pivotal in both neural differentiation and synaptic homeostasis, and RA deficiency has been suggested to be linked with various neuropsychiatric and neurodegenerative diseases (44). Thus, the findings in this study may uncover Dock4 as a mediator of RA signaling during normal or diseased brain development.…”

Section: Discussionmentioning

confidence: 65%

The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics

Xiao

Peng

Wan

et al. 2013

Journal of Biological Chemistry

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Background: Dock4, a guanine nucleotide exchange factor for Rac1, is associated with neuropsychiatric diseases. Results: Dock4 regulates neurite differentiation in neuroblastoma cells and hippocampal neurons. Conclusion: Dock4 is an important regulator during neural differentiation. Significance: This study contributes to a better understanding of the molecular and cellular events during neural differentiation and may provide new insights into the molecular pathophysiology of neuropsychiatric diseases.

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Section: Discussionmentioning

confidence: 65%

The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics

Xiao

Peng

Wan

et al. 2013

Journal of Biological Chemistry

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“…Although RA is increasingly recognized as an active signaling molecule in the adult brain (25), little is known about how RA synthesis is regulated in the adult nervous system. Our previous work showed that regular basal Ca 2+ levels in neurons maintained by normal synaptic transmission is sufficient to suppress RA synthesis, and that a decrease in basal Ca 2+ levels stimulates RA synthesis (6).…”

Section: Discussionmentioning

confidence: 99%

Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

Arendt

Zhang

Ganesan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.

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“…The expression of CALM and RBP1, gene products known to affect neuronal plasticity, was affected by stress or stress and time of emergence, respectively. Specifically, the protein RBP1 is implicated in the distribution of retinol (vitamin A), which in its active form (retinoic acid) is involved in the control of neural plasticity (for a review, see Shearer et al, 2012). CALM is a key protein in the transduction of signals in response to increases in intracellular Ca 2+ .…”

Section: Discussionmentioning

confidence: 99%

Natural selection constrains personality and brain gene expression differences in Atlantic salmon (Salmo salar)

Thörnqvist

Höglund

Winberg

2015

Journal of Experimental Biology

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In stream-spawning salmonid fishes there is a considerable variation in the timing of when fry leave the spawning nests and establish a feeding territory. The timing of emergence from spawning nests appears to be related to behavioural and physiological traits, e.g. early emerging fish are bolder and more aggressive. In the present study, emerging Atlantic salmon (Salmo salar L.) alevins were sorted into three fractions: early, intermediate and late emerging. At the parr stage, behaviour, stress responses, hindbrain monoaminergic activity and forebrain gene expression were explored in fish from the early and late emerging fractions (first and last 25%). The results show that when subjected to confinement stress, fish from the late emerging fraction respond with a larger activation of the brain serotonergic system than fish from the early fraction. Similarly, in late emerging fish, stress resulted in elevated expression of mRNA coding for serotonin 1A receptors (5-HT 1A ), GABA-A receptor-associated protein and ependymin, effects not observed in fish from the early emerging fraction. Moreover, fish from the early emerging fraction displayed bolder behaviour than their late emerging littermates. Taken together, these results suggest that time of emergence, boldness and aggression are linked to each other, forming a behavioural syndrome in juvenile salmon. Differences in brain gene expression between early and late emerging salmon add further support to a relationship between stress coping style and timing of emergence. However, early and late emerging salmon do not appear to differ in hypothalamus-pituitary-interrenal (HPI) axis reactivity, another characteristic of divergent stress coping styles.

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A vitamin for the brain

Cited by 125 publications

References 110 publications

The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics

The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics

Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

Natural selection constrains personality and brain gene expression differences in Atlantic salmon (Salmo salar)

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