Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234)

Zharkovsky A. Neural Cell Adhesion Molecule and its Possible Roles in Depression. Proceedings of the III Congress of Pharmacology Russia, Saint-Petersburg, 23–27 September 2007. Abstr 234. Psychopharmacol Biol Narcol 2007 Sept; 7 Suppl (Pt 1, A–L): 1-1695–1-1696Recent years much attention was put on the role brain plasticity in relation to depressive state. Neural cell adhesion (NCAM) plays important roles in the structural and functional plasticity in the CNS. If the reduced neuronal plasticity is an important factor predisposing to the development of depression, than animals with reduced brain plasticity due to deficiency in NCAM should serve as a valuable model of depression. Mice deficient in NCAM molecule demonstrated signs of depression-like behavior in the tail suspension and sucrose consumption tests. This was accompanied by the impaired object recognition in the object recognition test and the reduced levels of innate anxiety. Analysis of hippocampal neurogenesis in NCAM deficient mice revealed a reduced survival of the newborn cells and their differentiation into calbindin-positive granule neurons. The NCAM-/-mice demonstrated an increased fos B expression in the basolateral nucleus of amygdala, but not in other regions like dentate gyrus of hippocampus or piriform cortex. Since BDNF signaling system plays a significant role in the mechanisms of depression and in the effects of antidepressants, we measured the levels of BDNF and the level of phosphorylation of TrkB receptor in the brain of NCAM-/-mice. Experiments demonstrated a reduced BDNF signaling in the brains of NCAM-/-mice as a reduced level of phosphorylated Trk B receptor evidenced it. The depression-like signs in NCAM-/-mice were reversed by he acute or repeated administration of NCAM-mimetic peptide FGL. In addition, repeated FGL administration tended to reduce fos B activation in the basolateral nucleus of amygdala and enhanced survival of the newly generated cells in the dentate gyrus of NCAM-/-mice. The effects of FGL on the Trk B receptor phosphorylation are currently being studied in our laboratory. Our data suggest that reduced brain plasticity due to deficiency in NCAM gene plays a role in the development of depressive state and NCAM mimetic peptide FGL might represent a new class of drugs with antidepressant activity.Zharkovsky A. Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234

Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234)

Zharkovsky A. Neural Cell Adhesion Molecule and its Possible Roles in Depression. Proceedings of the III Congress of Pharmacology Russia, Saint-Petersburg, 23–27 September 2007. Abstr 234. Psychopharmacol Biol Narcol 2007 Sept; 7 Suppl (Pt 1, A–L): 1-1695–1-1696Recent years much attention was put on the role brain plasticity in relation to depressive state. Neural cell adhesion (NCAM) plays important roles in the structural and functional plasticity in the CNS. If the reduced neuronal plasticity is an important factor predisposing to the development of depression, than animals with reduced brain plasticity due to deficiency in NCAM should serve as a valuable model of depression. Mice deficient in NCAM molecule demonstrated signs of depression-like behavior in the tail suspension and sucrose consumption tests. This was accompanied by the impaired object recognition in the object recognition test and the reduced levels of innate anxiety. Analysis of hippocampal neurogenesis in NCAM deficient mice revealed a reduced survival of the newborn cells and their differentiation into calbindin-positive granule neurons. The NCAM-/-mice demonstrated an increased fos B expression in the basolateral nucleus of amygdala, but not in other regions like dentate gyrus of hippocampus or piriform cortex. Since BDNF signaling system plays a significant role in the mechanisms of depression and in the effects of antidepressants, we measured the levels of BDNF and the level of phosphorylation of TrkB receptor in the brain of NCAM-/-mice. Experiments demonstrated a reduced BDNF signaling in the brains of NCAM-/-mice as a reduced level of phosphorylated Trk B receptor evidenced it. The depression-like signs in NCAM-/-mice were reversed by he acute or repeated administration of NCAM-mimetic peptide FGL. In addition, repeated FGL administration tended to reduce fos B activation in the basolateral nucleus of amygdala and enhanced survival of the newly generated cells in the dentate gyrus of NCAM-/-mice. The effects of FGL on the Trk B receptor phosphorylation are currently being studied in our laboratory. Our data suggest that reduced brain plasticity due to deficiency in NCAM gene plays a role in the development of depressive state and NCAM mimetic peptide FGL might represent a new class of drugs with antidepressant activity.Zharkovsky A. Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234