Changes Of BDNF And TrkBmRNA Expression In Medial Septum Of Aged Rats And Effect Of Ginsenosides On Them

PrefaceIt has been thought that basal forebrain plays an important role in learning and memory. The medial septum (MS) , one of the important nucleus of basal forebrain, has built widely nerve fiber relation with hippocampus which is central nervous system ( CNS) about learning and memory by the cholinergic system and GABAnergic system pathways. Changes in morphology and function of the MS neurons would effect the animal's ability of learning and memory. BDNF, one of the neurotrophin family, is thought to be involved in neuronal survival, development, differentiation and modulation, most of which are mediated by the tyrosine receptor kinase, TrkB. Both BDNF and TrkB are widely expressed in CNS. But changes of BDNF and its receptor TrkB in MS during aging has not been well known. Therefore, we decided to investigate the changes of BDNF and its high affility receptor trkB in MS during normal aging.Ginsengs are conventional anti — aging and nootropic effect drugs. Its major composition is Ginsenosides ( GS) , which have positive effect on the nervous system in the age. However, the mechanism of GS has not been exactly understood at present. Some researchers have suggested that GS Rb1 could increase ChAT in basal forebrain cholinergic neurons and enhance NGFmRNA expression in hippocampus. But the study that whether GS could prevent neurons degeneration in MS by improving the expression of neurotrophins and their receptor are very limited. In the present study, we study the regulative mechanism of GS on CNS by investigating effects GS on BDNF and TrkB mRNA expression in the MS.Methods24 wistar rats were randomly divided into 3 groups: young group (3months) , aged group (27 months) and GS -treated group (27 months). GS- treated group was fed with GS from 17 to 27 months with water daily.Immunohistochemistry and imaging analysis were used to investigate the age- related changes and the effects GS on BDNF in MS. In situ hybridization and imaging analysis were used to investigate the age - related changes and the effects GS on TrkB mRNA expression in MS.Results1. Immunohistial chemistry1. 1 Investigation with microscopesIn MS neurons BDNF positive produces are stained yellow, most of them expressed primarily in the membrane of cell bodies and neuritis. Staining density in the young groups was higher than in the aged groups. Morphololgy of neurons in aged group is not very clear. And some cells in aged group appear atrophy, smaller than them of in the young. Saining density in GS - treated group was higher than that in aged groups. A number of the cells in MS of GS - treated becomes more than that of aged groups, and morphology becomes normal.1. 2 Quantitative analysisCompared with young groups, average grey valve of BDNF positive produces in MS neurons of aged groups is significantly higher (p <0. 01) , which showed that BDNF of MS neurons in aged groups are less than that of in young groups. And average grey value of BDNF positive produces in GS — treated is less than that of in aged groups, which suggested that compared with aged group, BDNF expression of MS neurons is increasing in GS -treated.2. In situ hybridization2.1 Investigation with microscopesIn MS neurons TrkBmRNA positive produces are stained yellow, most ofthem expressed primarily in the cytoplasm of cell. Morphololgy of neurons in each group is mostly clear. Staining density in the young groups was higher than in the aged groups. And some cells in aged group appear atrophy, disappear, and their number are less than in the young. Saining density in GS - treated group was higher than in aged groups. A number of cells in MS of GS - treated becomes more than that of aged groups, and morphology becomes mostly normal.2. 2 Quantitative analysisCompared with young groups, average grey valve of TrkBmRNA positive produces in MS neurons of aged groups is significantly higher ( p < 0. 01 ) , which showed that TrkBmRNA expression of MS neurons in aged groups are less than that of in young groups. And average grey value of TrkBmRNA positive produces in GS - treated is less than that of in aged groups, which suggested that compared with aged group, TrkBmRNA expression of MS neurons is increasing in GS - treated.Conclusion1. BDNF and TrkB mRNA expression were significantly decreased in MS neurons of aged group.2. Ginsenosides could increase the BDNF and TrkB mRNA expression in MS neurons of aged rats, and suggested that ginsenosides could protect or improve BDNF and TrkB mRNA expression in neurons.3. Ginsenosides could prevent the degenerative changes of neurons in MS by protecting BDNF and trkB mRNA, which performed the function of anti - aging and nootropic effects for GS.