Iron and n-3 fatty acid depletion, alone and in combination, during early development provoke neurochemical changes, anhedonia, anxiety and social dysfunction in rats

Erna T Kemp; Lizelle Zandberg; Brian H Harvey; Cornelius M Smuts; Jeannine Baumgartner

doi:10.1080/1028415X.2023.2245615

Iron and n-3 fatty acid depletion, alone and in combination, during early development provoke neurochemical changes, anhedonia, anxiety and social dysfunction in rats

Nutr Neurosci. 2023 Aug 10:1-17. doi: 10.1080/1028415X.2023.2245615. Online ahead of print.

Authors

Erna T Kemp¹, Lizelle Zandberg¹, Brian H Harvey^{2

3

4}, Cornelius M Smuts¹, Jeannine Baumgartner^{1

5}

Affiliations

¹ Center of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
² School of Pharmacy and Center of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
³ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴ The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
⁵ Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

PMID: 37585720
DOI: 10.1080/1028415X.2023.2245615

Abstract

Objectives: Both iron and omega-3 (n-3) fatty acids (FA) play important roles in the development and functioning of the brain. We investigated the effects of n-3 FA and iron deficiencies, alone and in combination, during early development on behaviour and brain monoamines in rats. Methods: Using a 2-factorial design, female Wistar rats were randomly allocated to one of four diet groups: Control, n-3 FA deficient (n-3 FAD), iron deficient (ID), or n-3 FAD + ID. Females received these diets throughout mating, pregnancy and lactation. Offspring (n = 24/group; male:female = 1:1) continued on the same diet until post-natal day 42-45, and underwent a sucrose preference test (SPT), novel object recognition test, elevated plus maze (EPM) and social interaction test (SIT). Results: ID offspring consumed less sucrose in the SPT and spent more time in closed arms and less time in open arms of the EPM than non-ID offspring. In female offspring only, ID and n-3 FAD reduced time approaching and together in the SIT, with an additive effect of ID and n-3 FAD for even less time approaching and spent together in the n-3 FAD + ID group compared to controls. ID offspring had higher striatal dopamine and norepinephrine and lower frontal cortex dopamine concentrations. N-3 FAD and ID affected frontal cortex serotonin concentrations in a sex-specific manner. Conclusions: Our results suggest that ID and n-3 FAD during early development provoke anhedonia, anxiety and social dysfunction in rats, with potential additive and attenuating effects when combined. These effects may in part be attributed to disturbances in brain neurochemistry and may be sex-specific.

Keywords: Social behaviour; anxious behaviour; cognition; early development; iron deficiency; monoamines; n-3 fatty acid deficiency; psychiatric comorbidity.