The Protective Role of L-carnitine on Psychosocial Stress-induced Changes in Gene Expression and Protein Levels of Matrix Metalloproteinases, Serum Corticosterone in a Rat Model

CNS Neurol Disord Drug Targets. 2023;22(10):1518-1525. doi: 10.2174/1871527322666221005130026.

Abstract

Background: Psychosocial stress (STS) is a common stress in modern societies. Chronic STS is associated with the impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in memory. Matrix metalloproteinases (MMPs), a protein family of zinccontaining endopeptidases, are essential in neuro-inflammation and involved in neurodegenerative diseases. L-Car possessed neuroprotective, antioxidant, and anti-inflammatory properties and was shown to modulate MMPs.

Objective: The current study aimed to examine the protective effect of L-Carnitine (L-CAR) on STSinduced changes in serum corticosterone levels, MMP-2, -9, and -12 protein and mRNA expression in the hippocampus as a possible mechanism for L-CAR protective effect on STS-induced memory impairment.

Methods: The chronic STS and L-CAR (300 mg/kg/day, i.p) were simultaneously administered for 6 weeks to adult male Wistar rats. Serum corticosterone and protein levels of MMP-2, -9 and -12 were evaluated using ELISA. Real-Time PCR techniques were used to determine the mRNA levels of MMP-2, -9 and -12 in the hippocampus.

Results: The findings showed that serum corticosterone levels and MMP-2 and -9 protein levels were significantly increased (p<0.05) in the STS group compared to the control. Similarly, RT-PCR findings showed that the mRNA of those proteinases significantly increased (p<0.05) following the intruder method. On the other hand, the administration of L-CAR restored the alterations in corticosterone levels and MMPs gene and protein expression induced by chronic STS.

Conclusion: STS induced elevations in corticosterone and MMP-2 and -9 levels in the hippocampus. L-CAR, on the other hand, exhibited protective effects against the STS-induced changes in MMP-2 and -9.

Keywords: Gene; Hippocampus; L-carnitine; Metalloproteinases; Psychosocial stress; corticosterone; expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnitine* / pharmacology
  • Corticosterone*
  • Gene Expression
  • Humans
  • Male
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinases
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Stress, Psychological / drug therapy

Substances

  • Carnitine
  • Corticosterone
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinases
  • RNA, Messenger