Mitochondrial function and nitric oxide production in hippocampus and cerebral cortex of rats exposed to enriched environment

Lores‐Arnaiz, Silvia; Arnaiz, M.R. Lores; Czerniczyniec, Analía; Cuello, Marina Inés; Bustamante, Juanita

doi:10.1016/j.brainres.2010.01.017

Cited by 17 publications

(7 citation statements)

References 36 publications

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“…The possibility may exist that the decreased expression of mitochondria-related genes in the tumors of EE mice is due to the slower progression of tumors. Nevertheless, previous studies have demonstrated that EE could affect mitochondrial function in the cerebral cortex 31 and white adipose tissue 32 , supporting an intercellular effect of EE on mitochondria. Further experiments including the comparison of gene expression profile between large and small tumors within the control group will help to elucidate the impact of EE on mitochondria in tumor cells.…”

Section: Discussionmentioning

confidence: 88%

Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Gan

Fan

et al. 2015

Sci Rep

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Psycho-social stress has been suggested to influence the development of cancer, but it remains poorly defined with regard to pancreatic cancer, a lethal malignancy with few effective treatment modalities. In this study, we sought to investigate the impacts of enriched environment (EE) housing, a rodent model of “eustress”, on the growth of mouse pancreatic cancer, and to explore the potential underlying mechanisms through gene expression profiling. The EE mice showed significantly reduced tumor weights in both subcutaneous (53%) and orthotopic (41%) models, while each single component of EE (inanimate stimulation, social stimulation or physical exercise) was not profound enough to achieve comparative anti-tumor effects as EE. The integrative transcriptomic and proteomic analysis revealed that in response to EE, a total of 129 genes in the tumors showed differential expression at both the mRNA and protein levels. The differentially expressed genes were mostly localized to the mitochondria and enriched in the citrate cycle and oxidative phosphorylation pathways. Interestingly, nearly all of the mitochondria-related genes were down-regulated by EE. Our data have provided experimental evidence in favor of the application of positive stress or of benign environmental stimulation in pancreatic cancer therapy.

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Section: Discussionmentioning

confidence: 88%

Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Gan

Fan

et al. 2015

Sci Rep

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“…Microdomains of nNOS in neurons in subcellular compartments contribute to calcium homeostasis and have been found to regulate calcium handling in endoplasmic reticulum 24,25 and mitochondria. 26 In addition, we recently reported that mitochondria plays a major role in the depolarization evoked [Ca 2+ ] i difference observed between the young SHRs and WKY rats by reducing the mitochondrial membrane potential in the SHR sympathetic neurons. 9 Some of the physiological and pathological effects of NO result from its actions at the mitochondrial level.…”

Section: Perspectivesmentioning

confidence: 97%

Targeted Neuronal Nitric Oxide Synthase Transgene Delivery Into Stellate Neurons Reverses Impaired Intracellular Calcium Transients in Prehypertensive Rats

Nikiforova

et al. 2013

Hypertension

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Hypertension is associated with the early onset of cardiac sympathetic hyperresponsiveness and enhanced intracellular Ca(2+) concentration [Ca(2+)](i) in sympathetic neurons from both prehypertensive and hypertensive, spontaneously hypertensive rats (SHRs). Oxidative stress is a hallmark of hypertension, therefore, we tested the hypothesis that the inhibitory action of the nitric oxide-cGMP pathway on [Ca(2+)](i) transients is impaired in cardiac sympathetic neurons from the SHR. Stellate ganglia were isolated from young prehypertensive SHRs and age-matched normotensive Wistar-Kyoto rats. [Ca(2+)](i) was measured by ratiometric fluorescence imaging. Neurons from the prehypertensive SHR ganglia had a significantly higher depolarization evoked [Ca(2+)](i) transient that was also associated with decreased expression of neuronal nitric oxide synthase (nNOS), β1 subunit of soluble guanylate cyclase and cGMP when compared with the Wistar-Kyoto rat ganglia. Soluble guanylate cyclase inhibition or nNOS inhibition increased [Ca(2+)](i) in the Wistar-Kyoto rats but had no effect in SHR neurons. A nitric oxide donor decreased [Ca(2+)](i) in both sets of neurons, although this was markedly less in the SHR. A novel noradrenergic cell specific vector (Ad.PRSx8-nNOS/Cherry) or its control vector (Ad.PRSx8-Cherry) was expressed in sympathetic neurons. In the SHR, Ad.PRSx8-nNOS/Cherry-treated neurons had a significantly reduced peak [Ca(2+)](i) transient that was associated with increased tissue levels of nNOS protein and cGMP concentration compared with gene transfer of Ad.PRSx8-Cherry alone. nNOS inhibition significantly increased [Ca(2+)](i) after Ad.PRSx8-nNOS/Cherry expression. We conclude that artificial upregulation of stellate sympathetic nNOS via targeted gene transfer can directly attenuate intracellular Ca(2+) and may provide a novel method for decreasing enhanced cardiac sympathetic neurotransmission.

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“…On the other hand, conditions which modify synaptic plasticity are likewise accompanied by modification in nNOS protein expression (Lores‐Arnaiz et al . , , ). The expression of nNOS protein in subcellular fractions is altered after administration of several drugs.…”

Section: Discussionmentioning

confidence: 99%

The low affinity neurotensin receptor antagonist levocabastine impairs brain nitric oxide synthesis and mitochondrial function by independent mechanisms

Lores‐Arnaiz

Karadayian

Gutnisky

et al. 2017

Journal of Neurochemistry

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Neurotensin is known to inhibit neuronal Na , K -ATPase, an effect that is rescued by nitric oxide (NO) synthase inhibition. However, whether the neurotensinergic and the nitrergic systems are independent pathways, or are mechanistically linked, remains unknown. Here, we addressed this issue and found that the administration of low affinity neurotensin receptor (NTS2) antagonist, levocabastine (50 μg/kg, i.p.) inhibited NO synthase (NOS) activity by 74 and 42% after 18 h in synaptosomal and mitochondrial fractions isolated from the Wistar rat cerebral cortex, respectively; these effects disappeared 36 h after levocabastine treatment. Intriguingly, whereas neuronal NOS protein abundance decreased (by 56%) in synaptosomes membranes, it was enhanced (by 86%) in mitochondria 18 h after levocabastine administration. Levocabastine enhanced the respiratory rate of synaptosomes in the presence of oligomycin, but it failed to alter the spare respiratory capacity; furthermore, the mitochondrial respiratory chain (MRC) complexes I-IV activities were severely diminished by levocabastine administration. The inhibition of NOS and MRC complexes activities were also observed after incubation of synaptosomes and mitochondria with levocabastine (1 μM) in vitro. These data indicate that the NTS2 antagonist levocabastine regulates NOS expression and activity at the synapse, suggesting an interrelationship between the neurotensinergic and the nitrergic systems. However, the bioenergetics effects of NTS2 activity inhibition are likely to be independent from the regulation of NO synthesis.

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Mitochondrial function and nitric oxide production in hippocampus and cerebral cortex of rats exposed to enriched environment

Cited by 17 publications

References 36 publications

Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Enriched Environment Inhibits Mouse Pancreatic Cancer Growth and Down-regulates the Expression of Mitochondria-related Genes in Cancer Cells

Targeted Neuronal Nitric Oxide Synthase Transgene Delivery Into Stellate Neurons Reverses Impaired Intracellular Calcium Transients in Prehypertensive Rats

The low affinity neurotensin receptor antagonist levocabastine impairs brain nitric oxide synthesis and mitochondrial function by independent mechanisms

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