Mice over-expressing BDNF in forebrain neurons develop an altered behavioral phenotype with age.
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.
City University of New York, College of Staten Island, Staten Island, NY 10314, USA; New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. Electronic address: klw7fu@virginia.edu.
Kate L
KL
Weidner
City University of New York, College of Staten Island, Staten Island, NY 10314, USA; New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Diego F
DF
Buenaventura
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. Electronic address: kathryn.chadman@opwdd.ny.gov.
Kathryn K
KK
Chadman
D000375:Aging / Q000502:physiology* / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002659:Child Development Disorders, Pervasive; D003192:Compulsive Behavior / Q000503:physiopathology; D003863:Depression / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009483:Neuropsychological Tests; D010641:Phenotype; D016548:Prosencephalon / Q000254:growth & development / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology; D012919:Social Behavior
D019208:Brain-Derived Neurotrophic Factor
Autism; Behavioral phenotype; Brain derived neurotrophic factor; Social approach; Transgenic mice