Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection

Halliru Zailani; Wen-Lung Wang; Senthil Kumaran Satyanarayanan; Wei-Che Chiu; Wen-Chun Liu; Yi-Shan Sung; Jane Pei-Chen Chang; Kuan-Pin Su

doi:10.59249/YZLQ4631

Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection

Yale J Biol Med. 2024 Sep 30;97(3):349-363. doi: 10.59249/YZLQ4631. eCollection 2024 Sep.

Authors

Halliru Zailani^{1

2

3}, Wen-Lung Wang⁴, Senthil Kumaran Satyanarayanan⁵, Wei-Che Chiu^{6

7}, Wen-Chun Liu^{8

9}, Yi-Shan Sung¹, Jane Pei-Chen Chang^{1

10

11}, Kuan-Pin Su^{1

10

12

13}

Affiliations

¹ Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
² Graduate Institute of Nutrition, China Medical University, Taichung, Taiwan.
³ Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
⁴ Department of Psychiatry, An Nan Hospital, China Medical University, Tainan, Taiwan.
⁵ Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong, China.
⁶ Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan.
⁷ School of Medicine, Fu Jen Catholic University, Taipei, Taiwan.
⁸ Department of Education and Research, An Nan Hospital, China Medical University, Tainan, Taiwan.
⁹ Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan.
¹⁰ College of Medicine, China Medical University, Taichung, Taiwan.
¹¹ Child and Adolescent Psychiatry Division, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
¹² Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
¹³ An Nan Hospital, China Medical University, Tainan, Taiwan.

Abstract

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.

Keywords: Aquaporin-4; blood-brain barrier; inflammation; major depressive disorder; metalloproteinase-9; omega-3 polyunsaturated fatty acids.

Publication types

Review

MeSH terms

Animals
Blood-Brain Barrier* / drug effects
Blood-Brain Barrier* / metabolism
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / metabolism
Fatty Acids, Omega-3* / metabolism
Fatty Acids, Omega-3* / pharmacology
Humans
Inflammation / drug therapy
Inflammation / metabolism
Neuroinflammatory Diseases* / drug therapy
Neuroinflammatory Diseases* / metabolism
Neuroprotection

Substances

Fatty Acids, Omega-3