Deficit in prepulse inhibition in mice caused by dietary n-3 fatty acid deficiency

Abstract

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may be biosynthesized from a precursor alpha-linolenic acid (LNA) or obtained preformed in the diet. Dams were fed four diets with different levels of the various n-3 fatty acids during pregnancy and lactation, and their offspring were weaned to the same diets: "n-3 Deficient," containing (as % total fatty acids) 0.07% of LNA; "Low LNA" (0.4%); "High LNA" (4.8%); and a "DHA + EPA" diet, containing 0.4% of LNA, 2% DHA, and 2% EPA. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response in C57Bl6 mice. The n-3 Deficient and Low LNA diets caused a substantial deficit in PPI compared to the DHA + EPA diet, whereas the High LNA diet induced a less pronounced, but significant reduction of PPI. These are the first data that demonstrate a deficit in sensorimotor gating in rodents caused by an inadequate amount of the n-3 fatty acids in the diet. Our results differentiate the effects of a High LNA diet from one with added EPA and DHA even though the difference in brain DHA content is only 12% between these dietary groups.

Fig. 1

Brain fatty acid analysis of 12 wk old mice. Values are given as mean ± SEM (n=9 in each group). Different letters indicate statistical differences between groups. DHA, docosahexaenoic acid (22:6n-3); DPAn-6, docosapentaenoic acid (22:5n-6); ARA, arachidonic acid (20:4n6); DTA, docosatetraenoic acid (22:4n6).

Fig. 2

Prepulse inhibition of the acoustic startle response. Data (mean ± SEM) show percent prepulse inhibition of the startle response following presentation of prepulse-plus-pulse acoustic stimuli, n=12 in each group. Different letters indicate statistical differences between groups (repeated measures ANOVA followed by Tukey HSD test).

Fig. 3

Habituation of the acoustic startle response. Data (mean ± SEM) show ratio of the mean startle reactivity of the last, third block to that of the first block of six consecutive pulse-alone trials. n=12 in each group. * indicates statistical significance, p<0.05 (t-test).