Alexander Kulikov
Siberian Division of Russian Academy of Sciences, Russia
Title: Spatial learning in the Morris water maze in mice genetically different in the predisposition to catalepsy: The effect brain-derived neurotrophic factor
Biography
Biography: Alexander Kulikov
Abstract
Mice with hereditary disturbances of the behavior and the brain are effective tools for preclinical study of the mechanisms of psychotropic drug action. Catalepsy or exagerated freezing is a sign of grave brain dysfunctions. The main gene determining of about 20% of genetic variation of catalepsy has been mapped at the terminal fragment of mouse chromosome 13. This fragment has been transferred from the catalepsy-prone CBA/Lac line to the genome of a catalepsy-resistant AKR/J line and the AKR.CBA-D13Mit76 (D13) recombinant line has been bred. About 50% of D13 mice are cataleptics. Mice of this line show elevated expression of the Il-6 gene, coding the pro-inflammation cytokine interleukine-6, in the cortex and hippocampus and sensitivity to lipopolysaccharide. MRI revealed a reduction of the pituitary gland in D13 mice. Unlike AKR mice, D13 mice show a spatial learning deficit in the Morris water maze (MWM). An acute ivc administration of 300 ng of brain derived neurotrophic factor (BDNF) normalized the performance and memory retention in the MWM in D13 mice. These results indicated a possible association between the hereditary catalepsy, MWM performance, pituitary gland reduction, BDNF and level of Il-6 mRNA in the brain, although the relation between these characteristics seems to be more complex. Thus, AKR.CBA-D13Mit76 recombinant mouse line with deficit of spatial learning, is a promising model for study of the genetic and molecular mechanisms of learning disorders as well as for screening potential cognitive enhancers.