Maternal consumption of a diet lacking omega‐3 fatty acids during development alters pup behavior and brain metabolism later in life
Authors: Jackson Corey , Alhado Mariam , Gonzales Elisa , Shumake Jason , Barrett Douglas , Gonzalez‐Lima Francisco , Lane Michelle A 
Published: November 2023

Rodent models have shown a relationship between omega‐3 fatty acid (n‐3FA) consumption and offspring behaviors related to anxiety, depression, and cognition. In these studies, offspring n‐3FA deficiency or supplementation continued after weaning, obscuring phenomena due solely to the developmental effects of maternal consumption of n‐3FAs during pregnancy and lactation. Our objective was to develop a rat model that allowed us to isolate the effects of gestational and perinatal n‐3FA deficiency and supplementation on offspring behavior and brain metabolic capacity. Female rats were fed diets formulated with 7% sunflower (−n‐3FA) or menhaden fish oil (+n‐3FA) for two cycles of gestation and lactation. Rat pups from the second reproductive cycle were weaned onto the animal facility diet, containing recommended n‐3FA levels, for five weeks prior to behavioral assessment and brain removal. Pups were tested in the open field (OF), forced swim (FS) and the holeboard (HB) tests to examine behaviors related to novelty reactivity and seeking, depression, and learning and memory, respectively. Brain metabolic capacity was assessed by quantitative cytochrome oxidase (CO) histochemistry. Maternal n‐3FA consumption did not affect behavior in the FS and HB tests. A diet x day interaction was observed in the OF test [F(1,16) = 4.625, P = 0.047]. Pups born to dams lacking n‐3FAs exhibited increased total ambulatory time (73.9 +/− 6.7 seconds) in the novel OF environment on day 1 when compared to pups whose dams consumed diets with n‐3FA (55.2 +/− 5.9 seconds). But the amount of ambulatory time in the familiar OF environment on day 2 was the same. Increased time spent moving in a novel (but not in a familiar) environment may indicate increased novelty reactivity. Pups in the –n‐3FA group spent more time in the center of the OF on both days than pups in the +n‐3FA group [F(1,16) = 5.829, P = 0.028], suggesting an increase in novelty‐seeking or risk‐taking behavior, as rats normally avoid the center of the OF. Maternal n‐3FA deficiency significantly decreased CO activity in the offspring's posterior cingulate cortex (P= 0.03), a cortical component of the limbic system involved in emotional behavior. There were also trends (P = 0.05) for increased CO activity in the nucleus accumbens shell and decreased CO activity in the cortical nucleus of the amygdala. These brain regions are often associated with emotional memories, reward‐seeking, defensive behavior and fear, respectively. We hypothesize that the increased ambulatory time exhibited by pups born to n‐3FA deficient mothers may be due to the decreased metabolism of the posterior cingulate cortex and cortical amygdala, which could lead to risk‐taking responses to the new environment. Increased metabolism in the accumbens shell might have also contributed to greater reward‐seeking in the new environment. In conclusion, changes in the n‐3FA content of the maternal diet during gestation and lactation alone, without alterations in offspring diet, can affect offspring emotional behavior and brain metabolism.Support or Funding InformationSupport for this project came from the Texas State University Research Enhancement and Developmental Leave Programs for ML.