Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex

Neuroscience. 2015 Feb 12:286:353-63. doi: 10.1016/j.neuroscience.2014.11.059. Epub 2014 Dec 8.


Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD).

Keywords: BDNF; DAT; animal model of mania; bipolar disorder; oxidative damage; trans fat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amphetamine
  • Animals
  • Bipolar Disorder / chemically induced
  • Bipolar Disorder / metabolism*
  • Bipolar Disorder / psychology*
  • Brain Chemistry
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebral Cortex / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Fatty Acids, Omega-3 / analysis
  • Fatty Acids, Omega-6 / analysis
  • Female
  • Fish Oils
  • Male
  • Motor Activity
  • Pregnancy
  • Protein Carbonylation
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species
  • Soybean Oil
  • Trans Fatty Acids / analysis
  • Trans Fatty Acids / toxicity*


  • Brain-Derived Neurotrophic Factor
  • Dopamine Plasma Membrane Transport Proteins
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fish Oils
  • Reactive Oxygen Species
  • Trans Fatty Acids
  • Soybean Oil
  • Amphetamine