Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks

Koga, Yusuke; Takahashi, Hirokazu; Oikawa, Daichi; Tachibana, Tetsuya; Denbow, D. Michael; Furuse, Mitsuhiro

doi:10.1016/j.neuroscience.2005.01.004

Cited by 65 publications

(43 citation statements)

References 28 publications

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“…Guanidinoacetic acid (1) could not distinguish between these receptor populations and the concentrations required in cerebellar granule cells (mM concentrations) may not be reached in GAMT deficiency [36] compared to concentrations required in cortical neurons. Interestingly, creatine had no effect as an agonist, antagonist or modulator despite suggestions that it interacts with GABA-benzodiazepine receptor complexes in chicks [37].…”

Section: Discussionmentioning

confidence: 90%

Guanidino Acids Act as ρ1 GABAC Receptor Antagonists

et al. 2009

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GABA(C) receptors play a role in myopia, memory-related disorders and circadian rhythms signifying a need to develop potent and selective agents for this class of receptors. Guanidino analogs related to glycine, beta-alanine and taurine were evaluated at human rho(1)GABA(C) receptors expressed in Xenopus oocytes using 2-electrode voltage clamp methods. Of the 12 analogs tested, 8 analogs were active as antagonists and the remaining were inactive. (S)-2-guanidinopropionic acid (IC(50) = 2.2 microM) and guanidinoacetic acid (IC(50) = 5.4 microM; K (B) = 7.75 microM [pK (B) = 5.11 +/- 0.06]) were the most potent being competitive antagonists at this receptor. In contrast, the beta-alanine and GABA guanidino analogs showed reduced activity, indicating the distance between the carboxyl carbon and terminal nitrogen of the guanidino group is critical for activity. Substituting the C2-position of guanidinoacetic acid with various alkyl groups reduced activity indicating that steric effects may impact on activity. The results of this study contribute to the structure-activity-relationship profile required in developing novel therapeutic agents.

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Section: Discussionmentioning

confidence: 90%

Guanidino Acids Act as ρ1 GABAC Receptor Antagonists

et al. 2009

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“…Second, creatine promotes antioxidant effects at the level of neural cell membranes (Lawler et al, 2002; Sestilli et al, 2006, 2011). Third, creatine is a neuromodulator of GABA A and NMDA receptor activity (Almeida et al, 2006; Koga et al, 2005; Oliveira et al, 2008), and possibly interacts with serotonergic and dopaminergic systems (Allen et al, 2010; Agren and Niklasson, 1988). …”

Section: Discussionmentioning

confidence: 99%

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

Allen

D’Anci

Kanarek

et al. 2012

Pharmacology Biochemistry and Behavior

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The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies.

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“…Furthermore, creatine appears to be released from neurons by a depolarizationinduced, calcium-dependent mechanism (Almeida et al 2006) suggesting that it functions as a neuromodulator. In this regard, there have been reports that creatine may act as a partial agonist at the GABA-A receptor (Koga et al 2005;Almeida et al 2006) and may interact with the NMDA receptor (Royes et al 2008).…”

Section: Creatinementioning

confidence: 99%

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

Maddock

Buonocore

2011

Current Topics in Behavioral Neurosciences

225

196

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The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics,and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate(NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action,and allow clinical monitoring of the effects of interventions on brain metabolicmarkers

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Brain creatine functions to attenuate acute stress responses through GABAnergic system in chicks

Cited by 65 publications

References 28 publications

Guanidino Acids Act as ρ1 GABAC Receptor Antagonists

Guanidino Acids Act as ρ1 GABAC Receptor Antagonists

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

MR Spectroscopic Studies of the Brain in Psychiatric Disorders

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