Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

Mannelli, Lorenzo Di Cesare; Vivoli, Elisa; Salvicchi, Alberto; Schiavone, Nicola; Koverech, Aleardo; Messano, Masa; Nicolai, Raffaella; Benatti, Paola; Bartolini, Alessandro; Ghelardini, Carla

doi:10.1007/s00213-011-2326-0

Cited by 25 publications

(16 citation statements)

References 54 publications

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“…In addition, in the samples from the placebo arm of the study, octanoyland decanoyl-carnitines were up-regulated in NRs compared with Rs. While acyl-carnitines have antidepressant effects in elderly (Pettegrew et al, 2000;2002) and mice (Di Cesare Mannelli et al, 2011), increased concentrations in NRs may reflect a dysfunction in signalling of the mitochondrial acylcarnitine receptor. It is of interest to note that TML is synthesized from lysine by S-adenosyl-methionine (SAM) catalyzed N-methylation and that SAM is in turn synthesized from L-methionine.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks

Villaseñor

Ramamoorthy

Santos

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSE(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non-targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non-response. EXPERIMENTAL APPROACHPlasma samples from 22 BD patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo-controlled crossover study and the samples were obtained 230 min post-administration at which time the patients were categorized as responders or non-responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate. KEY RESULTSThe metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non-responders. CONCLUSIONS AND IMPLICATIONSThe results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial β-oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy.

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Section: Discussionmentioning

confidence: 99%

A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks

Villaseñor

Ramamoorthy

Santos

et al. 2014

British J Pharmacology

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“…Other literature data contribute to the concept of pleiotropicity of action for LAC antidepressant effects. It has been proposed that LAC may act as an antidepressant via increased levels of the glia-derived growth factor artemin [ 94 ]. Moreover, the drug can increase hippocampal levels of noradrenaline and serotonin, well established positive modulators of adult neurogenesis [ 80 , 82 , 95 ].…”

Section: Lac As a Novel Antidepressant Drug With Unique Propertiesmentioning

confidence: 99%

l-Acetylcarnitine: A Mechanistically Distinctive and Potentially Rapid-Acting Antidepressant Drug

Chiechio

Canonico

Grilli

2017

IJMS

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Current therapy of mood disorders has several limitations. Although a high number of drugs are clinically available, as of today, nearly two-thirds of individuals do not achieve full symptomatic remission after treatment with conventional antidepressants. Moreover, several weeks of drug treatment are usually required to obtain clinical effects, a limitation that has considerable clinical implications, ranging from high suicide risk to reduced compliance. The characteristic lag time in classical antidepressant effectiveness has given great impulse to the search for novel therapeutics with more rapid effects. l-acetylcarnitine (LAC), a small molecule of growing interest for its pharmacological properties, is currently marketed for treatment of neuropathic pain. Recent preclinical and clinical data suggested that LAC may exert antidepressant effects with a more rapid onset than conventional drugs. Herein, we review data supporting LAC antidepressant activity and its distinctive mechanisms of action compared with monoaminergic antidepressants. Furthermore, we discuss the unique pharmacological properties of LAC that allow us to look at this molecule as representative of next generation antidepressants with a safe profile.

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“…Interestingly, LPS did not alter the concentration of the neuronal factor BDNF but increased levels of ARTN, a factor of glial origin involved in depression signaling (Di Cesare Mannelli et al, 2011). B .…”

Section: Discussionmentioning

confidence: 99%

Bacopa monnieri as augmentation therapy in the treatment of anhedonia, preclinical and clinical evaluation

Micheli

Spitoni

Mannelli

et al. 2020

Phytotherapy Research

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Bacopa monnieri (L.) is widely used in Ayurvedic medicine as a neural tonic for improving intelligence and memory. Several studies highlighted its efficacy in neuropsychiatric diseases but there is no evidence regarding anhedonia. Aim of the present work was to preclinically and clinically test against anhedonia a standardized B. monnieri extract (20% bacosides). In a mouse model of a depressive‐like syndrome induced by lipopolysaccharide (LPS), the daily administration of the extract (50–200 mg kg−1, p.o.) for 1 week, dose‐dependently counteracted the immobility time in Porsolt and Tail suspension tests (p < .01). At the sucrose preference test (directly related to the ability for feeling pleasure) the extract treatment (100 and 200 mg kg−1) counteracted the reduction of sucrose intake induced by LPS (p < .01). Moreover, B. monnieri significantly reduced cytokines, cortisol, and artemin LPS‐dependent alterations in plasma while increased the brain‐derived neurotrophic factor levels (p < .05). The efficacy of the same extract was tested in a clinical study in which 42 patients with significant degree of anhedonia (evaluated as Snaith‐Hamilton Pleasure Scale [SHAPS] score ≥ 3) were enrolled. Patients were divided into two groups and treated with citalopram or citalopram associated with B. monnieri (300 mg bid) for 4 weeks. The Pears Sample T‐test showed a significant improvement (p < .05) in relevant scales (Hamilton depression rating scale, SHAPS, and strength and difficulties questionnaire) in the extract‐treated group in comparison to citalopram alone was recorded. These data suggest that B. monnieri extract may be effective for the management of anhedonia and therefore should be considered for future controlled trials.

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Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

Abstract: A mechanism for the antidepressant property of ALCAR is proposed, and the novelty of the possible role of ARTN in depression is suggested.

Cited by 25 publications

References 54 publications

A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks

A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response‐related difference in mitochondrial networks

l-Acetylcarnitine: A Mechanistically Distinctive and Potentially Rapid-Acting Antidepressant Drug

Bacopa monnieri as augmentation therapy in the treatment of anhedonia, preclinical and clinical evaluation

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