&lt;b&gt;Neurotrophins in Neuroendocrine Control: Brain Derived-neurotrophic Factor (BDNF) and Somatostatin Involvement in the Stress Response and Reproductive Physiology &lt;b/&gt;

Arancibia, Sandor; Rage, Florence; Givalois, Laurent; Tapia‐Arancibia, Lucía

doi:10.5016/1806-8774.2003v5p5

Cited by 1 publication

(1 citation statement)

References 97 publications

(113 reference statements)

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“…It was previously reported that low concentrations of DNP increase cyclic AMP levels in cultured neurons (Wasilewska-Sampaio et al 2005) which, in addition to Ca 2+ , would also be expected to activate CREB and up-regulate BDNF expression. BDNF regulates neuronal energy metabolism and stress responses (Nakagawa et al 2002;Arancibia et al 2003;Larsen et al 2010;Marosi and Mattson 2014). BDNF can enhance glucose uptake and mitochondrial biogenesis in neurons, which may contribute to its important roles in synaptic plasticity and neuroprotection (Burkhalter et al 2003;Cheng et al 2012).…”

Section: Discussionmentioning

confidence: 99%

The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up‐regulation

Liu

Zhang

Gharavi

et al. 2015

Journal of Neurochemistry

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Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2, 4-dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increases intracellular Ca2+ levels and reduces oxidative stress in cerebral cortical neurons. Gene expression profiling of the cerebral cortex of DNP-treated mice revealed reprogramming of signaling cascades that included suppression of the mTOR and insulin – PI3K – MAPK pathways, and up-regulation of tuberous sclerosis complex 2, a negative regulator of mTOR. Genes encoding proteins involved in autophagy processes were up-regulated in response to DNP. CREB (cAMP-response element-binding protein) signaling, Arc and BDNF, which play important roles in synaptic plasticity and adaptive cellular stress responses, were up-regulated in response to DNP, and DNP-treated mice exhibited improved performance in a test of learning and memory. Immunoblot analysis verified that key DNP-induced changes in gene expression resulted in corresponding changes at the protein level. Our findings suggest that mild mitochondrial uncoupling triggers an integrated signaling response in brain cells characterized by reprogramming of mTOR and insulin signaling, and up-regulation of pathways involved in adaptive stress responses, molecular waste disposal and synaptic plasticity.

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