Nerve growth factor and phorbol esters increase the number of choline acetyltransferase-positive cells in two morphologically distinct classes of basal forebrain neurons in primary cultures.

Nerve growth factor (NGF) has been shown to be active in the CNS as a neurotrophic agent. Cholinergic neurons of the basal forebrain are one cell type in the CNS which have been identified as a target for NGF. When dissociated cell cultures from the basal forebrain were treated for 7 days with NGF (20 ng/100 microliters), the number of choline acetyltransferase (ChAT)-immunopositive cells was increased from 30 +/- 6 to 58 +/- 3. Cholinergic cells taken from the basal forebrain exhibit 3 different morphologies: stellate, pyramidal, and bipolar. The NGF treatment was found to increase the number of stellate cells from 7 +/- 2 to 23 +/- 2 and the number of pyramidal cells from 14 +/- 2 to 26 +/- 2, but had no effect on the number of bipolar cells. The activation of protein kinase C by phorbol 12-myristate, 13-acetate (TPA) also increased the number of ChAT-positive cells in a dose-dependent manner. A maximal increase was observed with 10 ng/ml of TPA which increased the number of positive cells from a basal level of 21 +/- 4 to 42 +/- 4. As was the case with NGF, only the stellate and pyramidal cells were affected by the phorbol ester treatment. In co-addition experiments, the cultures were treated with 10 ng/100 of NGF and 10 ng/ml of TPA, with the result that there was no further increase in the number of immunopositive cells over the NGF controls. These results suggest that the mechanisms by which NGF and TPA increase the number of ChAT-positive cells are interactive at some point. The effect of TPA at the higher doses of NGF was distinctly different. When cells were treated with 20 ng/100 microliters of NGF and 0.05-50 ng/ml of TPA, the NGF response was down-regulated to the level of the vehicle-treated controls.

[Protective effect of nerve growth factor on cholinergic neurons corpus striatum of new born rat subjected to hypoxia-ischemia].

Cerebral hypoxia-ischemia was produced in 7 day old rats by right common carotid artery occlusion combined with systemic hypoxia. In the hypoxic-ischemic group animals, striatal ACh contents on both sides were reduced to a significant extent in commensurate to AChE histochemical image analysis. All these changes could be restored to normal control by a protection dose (50 micrograms) of NGF intraventricularly injected.

[Resistant action of gangliosides on the 6-OHDA injured sympathetic nerves].

A single dose of 6-OHDA (15 mg/kg i.p.) would cause an almost complete disappearance of catecholamine fluorescence in histological preparation of submandibular glands (SMG) 24 hours after injection. Recovery of NA and DA levels went on slowly along with the course of regeneration of the lesioned sympathetic nerve terminals. The NA and the DA contents reached 50% and 28% respectively two weeks after lesion and fully recovered by the end of the fourth week. Gangliosides mixture (GM) (50 mg/kg i.p.) given 0, 4, 8, and 12 hours after 6-OHDA injection could prevent the injury action of NA and DA for at least 24 hours. If this treatment was followed by daily injection for one week, the NA contents remained normal by the end of two weeks. GM treatments beginning either 4 days before or 4 hours after 6-OHDA injection could lessen the extent of decrease of NA and DA by 6-OHDA. The results suggest that: a) GM is effective in protecting the membrane of sympathetic terminals from the injurious effect of 6-OHDA or 6-OHDA metabolites and promoting the regeneration of the lesioned terminals. b) The earlier the GM treatments are given, the better will be the effects.

[Influence of septohippocampal lesion on the levels of some neurotransmitters and enzymes in the rat hippocampus].

Partial deafferentation of the hippocampus was obtained by transection of unilateral partial fimbria-fornix. On the seventh postoperational day, there appeared in the lesioned hippocampus respectively a 72.5%, 45.7% and 52.2% reduction in acetylcholine content, choline acetyltransferase and cholinesterase activity. A concomitant 16.3%, 31.1% and 30.3% reduction in noradrenaline, dopamine and serotonin content respectively was also observed, while amino acids content did not show any change. The results indicate that the cholinergic and monoaminergic afferents of the hippocampal formation in the rat reach their target regions via the fimbria-fornix.