Growth factor effects on survival and development of calbindin immunopositive cultured septal neurons.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia, senile plaques, fibrillary tangles, and a reduction of cholinergic neurons in areas of the brain, including the septal nucleus. Certain growth factors may promote the long-term survival of this subpopulation of neurons at risk. This study was undertaken to characterize growth factors' long-term effects on survival and development of neurons expressing the calcium-binding protein calbindin. In order to accomplish this, embryonic day 16 rat septal neurons were grown in bilaminar culture with astrocytes and in the absence of serum. These cultures were chronically treated with estrogen (Es), insulin-like growth factors I/II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF). Insulin-like growth factor II significantly increased the number of neurons immunoreactive for calbindin by 155%, suggesting either an increase in the survival of this subpopulation or an increase in the percentage of cells expressing calbindin. Chronic treatment with NGF, IGF-II, and Es significantly increased the number of primary neuritic processes on calbindin-positive neurons, whereas NGF and Es caused significant increases in the number of secondary processes and in the total lengths of the neuritic processes. Thus, effects of IGF-II, estrogen, and NGF on survival and maintenance of this neuronal subpopulation may be dependent on alterations in neurons which are immunopositive for calbindin.

Effects of growth factors and estrogen on the development of septal cholinergic neurons from the rat.

Cholinergic neurons of the septum are preferentially subject to degeneration in Alzheimer's disease. There is evidence that nerve growth factor, basic fibroblast growth factor, insulin-like growth factors, and estrogen all have effects on survival of this specific population of neurons at risk. We used a bilaminar culturing method to grow embryonic septal neurons from the rat in the presence of a separate glial plane but in the absence of serum. These neurons were treated with a number of factors, and neurite development of cholinergic neurons was assessed. Basic fibroblast growth factor and estrogen altered the number of primary neurites, number of secondary neurites, and mean total neurite lengths, while none of the other factors affected these end points. This would suggest a mechanism for the effects of these factors on memory.