Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization

Semanur Güner; Elif Beyzanur Polat; Hümeysa Kiyak-Kırmacı; Hatice Kübra Elçioğlu

Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization

Abstract

Neuroinflammation is a key pathological process underlying the progression of various neurological disorders, with microglia serving as the primary immune regulators of the central nervous system. Depending on their activation state and phenotypic profile, microglia can exert either neurotoxic or neuroprotective effects. In this context, understanding the mechanisms that regulate microglial activation and polarization has become a critical area of research. This mini-review compiles findings from in vitro, in vivo, and clinical studies identified through a comprehensive literature search focusing on the effects of citicoline on microglial activation and phenotypic polarization. Citicoline, a well-established neuroprotective agent, has been shown to modulate multiple pathways, including cholinergic signaling, oxidative stress, and inflammatory responses. Evidence from experimental and clinical studies indicates that citicoline reduces neuroinflammation by downregulating pro-inflammatory mediators such as TNF-α, IL-1β, and IL-6, while in some contexts increasing anti-inflammatory markers such as IL-10. Studies investigating the neuroprotective effects of citicoline further suggest its potential role in shifting microglial activity toward a more neuroprotective phenotype, characterized by decreased expression of M1-associated markers and increased expression of M2-associated markers. However, findings across studies remain inconsistent, largely due to differences in experimental models, treatment protocols, and outcome measures. Moreover, it is still unclear whether the observed effects are mediated through direct modulation of microglial cells or indirectly via alterations in the broader neuroinflammatory microenvironment. This review highlights these mechanistic uncertainties and underscores the need for cell-specific investigations to refine citicoline-based therapeutic strategies for neurological disorders.

Keywords

Project Number

1649B022404820

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Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Review

Authors

Semanur Güner
0000-0001-9299-9699
Türkiye

Elif Beyzanur Polat
0000-0002-3093-3595
Türkiye

Hümeysa Kiyak-Kırmacı
0000-0003-2574-4762
Türkiye

Hatice Kübra Elçioğlu ^*
0000-0001-6386-1711
Türkiye

Publication Date

August 3, 2026

Submission Date

April 22, 2026

Acceptance Date

July 23, 2026

Published in Issue

Year 2026 Volume: 30 Number: 4

IZ

https://izlik.org/JA84GF96RR

Cite

RIS / Bibtex

APA

Güner, S., Polat, E. B., Kiyak-Kırmacı, H., & Elçioğlu, H. K. (2026). Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization. Journal of Research in Pharmacy, 30(4), 1140-1147. https://izlik.org/JA84GF96RR

AMA

1.Güner S, Polat EB, Kiyak-Kırmacı H, Elçioğlu HK. Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization. J. Res. Pharm. 2026;30(4):1140-1147. https://izlik.org/JA84GF96RR

Chicago

Güner, Semanur, Elif Beyzanur Polat, Hümeysa Kiyak-Kırmacı, and Hatice Kübra Elçioğlu. 2026. “Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization”. Journal of Research in Pharmacy 30 (4): 1140-47. https://izlik.org/JA84GF96RR.

EndNote

Güner S, Polat EB, Kiyak-Kırmacı H, Elçioğlu HK (August 1, 2026) Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization. Journal of Research in Pharmacy 30 4 1140–1147.

IEEE

[1]S. Güner, E. B. Polat, H. Kiyak-Kırmacı, and H. K. Elçioğlu, “Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization”, J. Res. Pharm., vol. 30, no. 4, pp. 1140–1147, Aug. 2026, [Online]. Available: https://izlik.org/JA84GF96RR

ISNAD

Güner, Semanur - Polat, Elif Beyzanur - Kiyak-Kırmacı, Hümeysa - Elçioğlu, Hatice Kübra. “Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization”. Journal of Research in Pharmacy 30/4 (August 1, 2026): 1140-1147. https://izlik.org/JA84GF96RR.

JAMA

1.Güner S, Polat EB, Kiyak-Kırmacı H, Elçioğlu HK. Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization. J. Res. Pharm. 2026;30:1140–1147.

MLA

Güner, Semanur, et al. “Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization”. Journal of Research in Pharmacy, vol. 30, no. 4, Aug. 2026, pp. 1140-7, https://izlik.org/JA84GF96RR.

Vancouver

1.Semanur Güner, Elif Beyzanur Polat, Hümeysa Kiyak-Kırmacı, Hatice Kübra Elçioğlu. Citicoline and Microglial Activation: Modulation of Neuroinflammation and Phenotypic Polarization. J. Res. Pharm. [Internet]. 2026 Aug. 1;30(4):1140-7. Available from: https://izlik.org/JA84GF96RR