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Indian Journal of Pharmaceutical Education and ResearchNOW IN
Article

Modulatory Effects of Dietary Saturated Versus Omega-3 Fatty Acids on Cognitive Impairment, Depressive-Like Behavior, HPA Axis Dysregulation and Systemic Inflammation in Monosodium Glutamate-Treated Young Male Rats

Hebatallah Husseini Atteia1★, Amal F. Gharib2, Mervat El-Sayed Askar3, Manar Hamed Arafa4, Gehan A. Ahmed4, Amr Tawfik Sakr5★ Corresponding author

  1. 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, SAUDI ARABIA.
  2. 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, SAUDI ARABIA.
  3. 3Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Sharkia Governorate, EGYPT.
  4. 4Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Sharkia Governorate, EGYPT.
  5. 5Department of Biochemistry, Faculty of Pharmacy, University of Sadat City (USC), Menoufia, EGYPT.

CORRESPONDENCE

Hebatallah Husseini Atteia

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, SAUDI ARABIA.

hatteia@ut.edu.sa

Received: 28-01-2024; Revised: 14-03-2025; Accepted: 09-06-2025.

Volume 59, Issue 4 · pp. 1511–1521 · PUBLISHED 2025 · DOI: 10.5530/ijper.20251190

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ABSTRACT

Background and Objectives: Children consume fast food rich in saturated fats and flavor enhancers like Monosodium Glutamate (MSG). These agents might alter Hypothalamic-Pituitary- Adrenal (HPA) axis activity, inducing behavioral deficits. Consequently, we hypothesized that adding saturated fat to MSG-treated rats' diet could exaggerate their HPA axis response, behavioral deficits and systemic inflammation whereas dietary polyunsaturated omega-3 fatty acids could alleviate MSG-induced detrimental effects by affecting hypothalamic Glucocorticoid Receptor (GR) and microRNAs. Materials and Methods: To test current hypotheses, young male rats were gavaged with 3 g/kg MSG and concurrently fed either a normal or a 10% palm oil- or a 10% fish oil-enriched diet for 4 months. Results: Feeding saturated fats to MSG-treated rats aggravated HPA axis activation and hypothalamic GR down-regulation. They also worsened MSG-triggered cognitive impairment and depressive-like behavior. Saturated fats also amplified systemic inflammation by up-regulating hypothalamic Nuclear Factor kappa B (NFkB) and Toll-Like Receptor 4 (TLR4). Conversely, dietary omega-3 fatty acids significantly alleviated MSG-induced HPA axis activation and hypothalamic microRNA218 (miRNA218) up-regulation. Additionally, these fatty acids markedly ameliorated GR down-regulation. They also protected MSG-treated rats against cognitive dysfunction, depressive-like behavior and systemic inflammatory responses. Their anti-inflammatory potential was coupled with down-regulation of NFkB and TLR4 and up-regulation of miRNA155 in the hypothalamus. Conclusion: Thus, it is highly recommended to replace saturated with omega-3 fatty acids in fast foods to prevent MSG harmful effects on the HPA axis, particularly in children, after performing broad-scale clinical trials.

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    Atteia, H. H., Gharib, A. F., Askar, M. E., Arafa, M. H., Ahmed, G. A., & Sakr, A. T. (2025). Modulatory Effects of Dietary Saturated Versus Omega-3 Fatty Acids on Cognitive Impairment, Depressive-Like Behavior, HPA Axis Dysregulation and Systemic Inflammation in Monosodium Glutamate-Treated Young Male Rats. Indian Journal of Pharmaceutical Education and Research, 59(4), 1511–1521. https://doi.org/10.5530/ijper.20251190