Evidence map›Paper›PMID 35721218›Full record

ArticleFrontiers in pharmacology2022

Synergic action of L-acetylcarnitine and L-methylfolate in Mouse Models of Stress-Related Disorders and Human iPSC-Derived Dopaminergic Neurons.

Rosamaria Orlando, Roxana Paula Ginerete, Laura Cavalleri, Vincenza Aliperti, Tiziana Imbriglio, Giuseppe Battaglia, Anna Rita Zuena, Ferdinando Nicoletti, Emilio Merlo Pich, Ginetta Collo

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 43% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Rosamaria OrlandoIRCCS Neuromed, Pozzilli, Italy.
Roxana Paula GinereteIRCCS Neuromed, Pozzilli, Italy.
Laura CavalleriDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Vincenza AlipertiDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Tiziana ImbriglioIRCCS Neuromed, Pozzilli, Italy.
Giuseppe BattagliaIRCCS Neuromed, Pozzilli, Italy.
Anna Rita ZuenaDepartment of Physiology and Pharmacology, Sapienza University, Rome, Italy.
Ferdinando NicolettiIRCCS Neuromed, Pozzilli, Italy.
Emilio Merlo PichResearch and Development, Alfasigma S.p.A., Bologna, Italy.
Ginetta ColloDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Istituto Neurologico Mediterraneo · ITUniversity of Brescia · ITSapienza University of Rome · ITAlfasigma (Italy) · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The epigenetic agents, L-acetylcarnitine (LAC) and L-methylfolate (MF) are putative candidates as add-on drugs in depression. We evaluated the effect of a combined treatment with LAC and MF in two different paradigms of chronic stress in mice and in human inducible pluripotent stem cells (hiPSCs) differentiated into dopaminergic neurons. Two groups of mice were exposed to chronic unpredictable stress (CUS) for 28 days or chronic restraint stress (CRS) for 21 day, and LAC (30 or 100 mg/kg) and/or MF (0.75 or 3 mg/kg) were administered i.p. once a day for 14 days, starting from the last week of stress. In both stress paradigms, LAC and MF acted synergistically in reducing the immobility time in the forced swim test and enhancing BDNF protein levels in the frontal cortex and hippocampus. In addition, LAC and MF acted synergistically in enhancing type-2 metabotropic glutamate receptor (mGlu2) protein levels in the hippocampus of mice exposed to CRS. Interestingly, CRS mice treated with MF showed an up-regulation of NFκB p65, which is a substrate for LAC-induced acetylation. We could also demonstrate a synergism between LAC and MF in cultured hiPSCs differentiated into dopamine neurons, by measuring dendrite length and number, and area of the cell soma after 3 days of drug exposure. These findings support the combined use of LAC and MF in the treatment of MDD and other stress-related disorders.

Indexed as

BDNFchronic stressdepressionhiPSCL-acetylcarnitineL-methylfolatemGlu2 receptors

Identifiers

PMID35721218
PMCPMC9201783
OpenAlexW4281681959

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.