Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

Réus, Gislaine Z.; Stringari, Roberto B.; Rezin, Gislaine T.; Fraga, Daiane B.; Daufenbach, Juliana F.; Scaini, Giselli; Benedet, Joana; Rochi, Natália; Streck, Emílio L.; Quevedo, João

doi:10.1007/s00702-011-0718-2

Cited by 18 publications

(14 citation statements)

References 86 publications

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“…Furthermore, 4-methyl-2-oxopentanoate is often used to assess liver mitochondrial function and can influence glutamate synthesis in neurons [80, 81]. Several studies have implicated alterations in brain energetics in the pathogenesis of depression and effects of antidepressants [38, 82, 83]. Consistent with these observations, our results suggest a model in which subtle alterations in mitochondrial bioenergetics may contribute to the pathophysiology of depressive symptoms.…”

Section: Discussionsupporting

confidence: 87%

Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression

Cassol

Misra

Morgello

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood. Methods The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across three independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R. Results Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of IFN responses, suggesting inter-relationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection. Conclusions Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for prevention and treatment of depression in people with and without HIV.

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Section: Discussionsupporting

confidence: 87%

Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression

Cassol

Misra

Morgello

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Interestingly, a study by Assis et al (2009) showed that the acute administration of ketamine, besides producing an anti-immobility effect, increased the creatine kinase activity in striatum, cerebral cortex and cerebellum. Memantine, another NMDAR antagonist with anti-immobility effect, also increased creatine kinase activity in prefrontal cortex and hippocampus of rats (Reus et al 2012). In vitro and in vivo studies have reported that ketamine and MK-801 facilitate recovery of phosphocreatine levels after ischemic or anoxic brain injury, clinical conditions associated with glutamatergic dysfunction (Bielenberg et al 1987;Haraldseth et al 1990;Raley and Lipton 1990;Spandou et al 1999).…”

Section: Discussionmentioning

confidence: 97%

The modulation of NMDA receptors and l-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test

et al. 2015

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The modulation of N-methyl-D-aspartate receptor (NMDAR) and L-arginine/nitric oxide (NO) pathway is a therapeutic strategy for treating depression and neurologic disorders that involves excitotoxicity. Literature data have reported that creatine exhibits antidepressant and neuroprotective effects, but the implication of NMDAR and L-arginine/nitric oxide (NO) pathway in these effects is not established. This study evaluated the influence of pharmacological agents that modulate NMDAR/L-arginine-NO pathway in the anti-immobility effect of creatine in the tail suspension test (TST) in mice. The NOx levels and cellular viability in hippocampal and cerebrocortical slices of creatine-treated mice were also evaluated. The anti-immobility effect of creatine (10 mg/kg, po) in the TST was abolished by NMDA (0.1 pmol/mouse, icv), D-serine (30 µg/mouse, icv, glycine-site NMDAR agonist), arcaine (1 mg/kg, ip, polyamine site NMDAR antagonist), L-arginine (750 mg/kg, ip, NO precursor), SNAP (25 μg/mouse, icv, NO donor), L-NAME (175 mg/kg, ip, non-selective NOS inhibitor) or 7-nitroindazole (50 mg/kg, ip, neuronal NOS inhibitor), but not by DNQX (2.5 µg/mouse, icv, AMPA receptor antagonist). The combined administration of sub-effective doses of creatine (0.01 mg/kg, po) and NMDAR antagonists MK-801 (0.001 mg/kg, po) or ketamine (0.1 mg/kg, ip) reduced immobility time in the TST. Creatine (10 mg/kg, po) increased cellular viability in hippocampal and cerebrocortical slices and enhanced hippocampal and cerebrocortical NO x levels, an effect potentiated by L-arginine or SNAP and abolished by 7-nitroindazole or L-NAME. In conclusion, the anti-immobility effect of creatine in the TST involves NMDAR inhibition and enhancement of NO levels accompanied by an increase in neural viability.

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“…In the case of mixed or dual uptake inhibitors, four weeks of either clomipramine (Anafranil) or tianeptine (Stablon) have been shown to normalize total creatine in the forebrain of stressed tree shrews (Czéh et al, 2001; Fuchs et al, 2002; van der Hart et al, 2002), four weeks of desipramine (Norpramine) increased total creatine in the DLPFC of male C57BL/6 mice (Kim et al, 2010), and acute imipramine (Tofranil) increased creatine kinase activity in the striatum, cerebellum, and PFC of rats (Assis et al, 2009; Réus et al, 2011, 2012). For atypical antipsychotics, acute treatment with aripiprazole (Abilify) or olanzapine (Zyprexa) increased creatine kinase activity in the striatum and cerebellum (Assis et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

Allen

2012

Neuroscience & Biobehavioral Reviews

152

135

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Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington’s Disease and Parkinson’s Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies.

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Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain

Cited by 18 publications

References 86 publications

Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression

Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression

The modulation of NMDA receptors and l-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

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