Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria

Katyare, Surendra S.; Rajan, Rehim N.

doi:10.1016/0742-8413(95)02031-4

Cited by 23 publications

(19 citation statements)

References 14 publications

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“…Thus, their altered level in the CLO depression model suggests that energy production may be affected in depression. Indeed, chronic administration of the tricyclic antidepressant imipramine in rats resulted in altered respiratory rates and increased ATP synthesis in brain mitochondria [39]. The significance of the correlation between mitochondrial functions and MDD has been emphasized recently [40,41], and our results are consistent with this correlation.…”

Section: Accepted M Manuscriptsupporting

confidence: 82%

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

Gellén

Völgyi

Győrffy

et al. 2017

Journal of Proteomics

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Section: Accepted M Manuscriptsupporting

confidence: 82%

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

Gellén

Völgyi

Győrffy

et al. 2017

Journal of Proteomics

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“…Electroconvulsive therapy and transcranial magnetic stimulation similarly enhance mitochondrial function (Dragicevic et al 2011). In the rat, chronic treatment with imipramine stimulated state 3 and 4 respiration rates (Katyare and Rajan 1995). There is also evidence that antidepressants protect mitochondria against various injuries including O&NS.…”

Section: Mitochondria As New Drug Targets In Depressionmentioning

confidence: 98%

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

Maes

Fišar

Medina³

et al. 2012

Inflammopharmacol

293

196

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This paper reviews new drug targets in the treatment of depression and new drug candidates to treat depression. Depression is characterized by aberrations in six intertwined pathways: (1) inflammatory pathways as indicated by increased levels of proinflammatory cytokines, e.g. interleukin-1 (IL-1), IL-6, and tumour necrosis factor α. (2) Activation of cell-mediated immune pathways as indicated by an increased production of interferon γ and neopterin. (3) Increased reactive oxygen and nitrogen species and damage by oxidative and nitrosative stress (O&NS), including lipid peroxidation, damage to DNA, proteins and mitochondria. (4) Lowered levels of key antioxidants, such as coenzyme Q10, zinc, vitamin E, glutathione, and glutathione peroxidase. (5) Damage to mitochondria and mitochondrial DNA and reduced activity of respiratory chain enzymes and adenosine triphosphate production. (6) Neuroprogression, which is the progressive process of neurodegeneration, apoptosis, and reduced neurogenesis and neuronal plasticity, phenomena that are probably caused by inflammation and O&NS. Antidepressants tend to normalize the above six pathways. Targeting these pathways has the potential to yield antidepressant effects, e.g. using cytokine antagonists, minocycline, Cox-2 inhibitors, statins, acetylsalicylic acid, ketamine, ω3 poly-unsaturated fatty acids, antioxidants, and neurotrophic factors. These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously. Both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways. GSK-3 inhibitors have antidepressant effects in animal models of depression. Nrf2 activators and GSK-3 inhibitors have the potential to be advanced to phase-2 clinical trials to examine whether they augment the efficacy of antidepressants or are useful as monotherapy.

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“…49 Data on oxidative energy metabolism suggest that IMI had a maximum stimulation of respiration in the brain mitochondria that was sustained after 1-and 2-week treatment. 50 It should however be noted that IMI at high concentrations can inhibit ATPase activity; 51 moreover, uncoupling effects on oxidative phosphorylation in rat liver mitochondria have been described with melipramine. 52 It is possible that the human ortholog of the gene represented in rat EST202275 is the mitochondrial 16S rRNA gene.…”

Section: Discussionmentioning

confidence: 99%

St John's wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response

Wong¹,

O'Kirwan²,

Hannestad³

et al. 2004

Mol Psychiatry

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Both the prototypic tricyclic antidepressant imipramine (IMI) and the herbal product St John's wort (SJW) can be effective in the treatment of major depressive disorder. We studied hypothalamic gene expression in rats treated with SJW or IMI to test the hypothesis that chronic antidepressant treatment by various classes of drugs results in shared patterns of gene expression that may underlie their therapeutic effects. Individual hypothalami were hybridized to individual Affymetrix chips; we studied three arrays per group treatment. We constructed 95% confidence intervals for expression fold change for genes present in at least one treatment condition and we considered genes to be differentially expressed if they had a confidence interval excluding 1 (or À1) and had absolute difference in expression value of 10 or greater. SJW treatment differentially regulated 66 genes and expression sequence tags (ESTs) and IMI treatment differentially regulated 74 genes and ESTs. We found six common transcripts in response to both treatments. The likelihood of this occurring by chance is 1.14 Â 10 À23 . These transcripts are relevant to two molecular machines, namely the ribosomes and microtubules, and one cellular organelle, the mitochondria. Both treatments also affected different genes that are part of the same cell function processes, such as glycolytic pathways and synaptic function. We identified single-nucleotide polymorphisms in the human orthologs of genes regulated both treatments, as those genes may be novel candidates for pharmacogenetic studies. Our data support the hypothesis that chronic antidepressant treatment by drugs of various classes may result in a common, final pathway of changes in gene expression in a discrete brain region.

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Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria

Cited by 23 publications

References 14 publications

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

St John's wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response

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