Mice over-expressing BDNF in forebrain neurons develop an altered behavioral phenotype with age

• After 5 months, BDNF over-expressing (BDNF-tg) mice weigh less than wildtype (WT) littermates.
• Aged BDNF-tg mice develop spontaneous seizures unlike WT.
• Aged BDNF-tg mice show less compulsive-like, anxiety-like and depressive-like behavior.
• Aged BDNF-tg mice demonstrate similar social behavior compared to WT.
• Aged BDNF-tg mice do not present an ASD behavioral phenotype.

Evidence from clinical studies suggests that abnormal activity of brain derived neurotrophic factor (BDNF) contributes to the pathogenesis of autism spectrum disorders (ASDs). A genetically modified line of mice over-expressing a BDNF transgene in forebrain neurons was used to investigate if this mutation leads to changes in behavior consistent with ASD. The mice used in these experiments were behaviorally tested past 5 months of age when spontaneous seizures were evident. These seizures were not observed in age-matched wildtype (WT) mice or younger mice from this transgenic line. The BDNF mice in these experiments weighed less than their WT littermates. The BDNF transgenic (BDNF-tg) mice demonstrated similar levels of sociability in the social approach test. Conversely, the BDNF-tg mice demonstrated less obsessive compulsive-like behavior in the marble burying test, less anxiety-like behavior in the elevated plus maze test, and less depressive-like behavior in the forced swim test. Changes in behavior were found in these older mice that have not been observed in younger mice from this transgenic line, which may be due to the development of seizures as the mice age. These mice do not have an ASD phenotype but may be useful to study adult onset epilepsy.