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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine.

ABSTRACT: Emerging evidence suggests that hierarchical status provides vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance in depressed patients. We investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically-stressed mice using 1H-magnetic resonance spectroscopy (1H-MRS). High rank, but not low rank, mice, as assessed with the tube test, showed behavioral vulnerability to stress, supporting a higher susceptibility of high social rank mice to develop depressive-like behaviors. High rank mice also showed reduced levels of several energy-related metabolites in the NAc that were counteracted by LAC treatment. Therefore, we reveal a metabolic signature in the NAc for antidepressant-like effects of LAC in vulnerable mice characterized by restoration of stress-induced neuroenergetics alterations and lipid function.

SUBMITTER: Cherix A

PROVIDER: S-EPMC6970538 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine.

Cherix Antoine A Larrieu Thomas T Grosse Jocelyn J Rodrigues João J McEwen Bruce B Nasca Carla C Gruetter Rolf R Sandi Carmen C

eLife 20200110

Emerging evidence suggests that hierarchical status provides vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance in depressed patients. We investigated the metabolic impac ...[more]

PMID: 31922486

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Project description:Context:Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. Objective:To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. Design:After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Setting:Five diabetology units and one clinical research center in Italy. Patients:Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine <1.5 mg/dL. Interventions:Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. Outcome and Measures:Primary outcome was SBP. Secondary outcomes included lipid and glycemic profiles. Total-body glucose disposal rate and glomerular filtration rate were measured in subgroups by hyperinsulinemic-euglycemic clamp and iohexol plasma clearance, respectively. Results:SBP did not significantly change after 6-month treatment with ALC compared with placebo (-2.09 mm Hg vs -3.57 mm Hg, P = 0.9539). Serum cholesterol, triglycerides, and lipoprotein(a), as well as blood glucose, glycated hemoglobin, fasting insulin levels, homeostatic model assessment of insulin resistance index, glucose disposal rate, and glomerular filtration rate did not significantly differ between treatments. Adverse events were comparable between groups. Conclusions:Six-month oral ALC supplementation did not affect blood pressure, lipid and glycemic control, insulin sensitivity and kidney function in hypertensive normoalbuminuric and microalbuminuric T2D patients on background statin therapy.

Dataset Information

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine.

Publications

Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine.

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