The effect of brain-derived neurotrophic factor on neuritogenesis and synaptic plasticity in Aplysia neurons and the hippocampal cell line HiB5

Brain-derived neurotrophic factor (BDNF) plays a key role in the differentiation and neuritogenesis of developing neurons, and in the synaptic plasticity of mature neurons, in the mammalian nervous system. BDNF binds to the receptor tyrosine kinase TrkB and transmits neurotrophic signals by activating neuron-specific tyrosine phosphorylation pathways. However, the neurotrophic function of BDNF in Aplysia neurons is poorly understood. We examined the specific effect of BDNF on neurite outgrowth and synaptic plasticity in cultured Aplysia neurons and a multipotent rat hippocampal stem cell line (HiB5). Our study indicates that mammalian BDNF has no significant effect on the neuritogenesis, neurotransmitter release, excitability, and synaptic plasticity of cultured Aplysia neurons in our experimental conditions. In contrast, BDNF in combination with platelet-derived growth factor (PDGF) increases the length of the neurites and the number of spine-like structures in cells of HiB5.     

Alteration of protein metabolism in individual,identified neurons from Aplysia

A search for control mechanisms governing protein metabolism in neurons from Aplysia californica has uncovered two examples of altered patterns of newly synthesized proteins: (1) The pattern of newly synthesized proteins in the R2 neuron is altered when protein synthesis occurs at elevated temperatures (22–30°C as compared with 13–15°C). (2) The processing of newly synthesized 12,000 dalton (12k) material to 6–9,000 dalton (6–9k) size in the R15 neuron (Strumwasser, F. and Wilson, D. F. [1976], J. Gen. Physiol., in press) can be blocked by certain ion replacements. If acetate replaces chloride in the incubation medium during the synthesis of 12k material, an early step in the processing, prior to the actual breakdown of 12k material, is blocked. Experiments with RNA-synthesis inhibitors indicate that none of the mRNAs which code for abundantly synthesized protein species in the R2 or R15 neurons have short (less than 4 hr) half-lives. This result has implications for an earlier report of regulation of protein synthesis in the R15 neuron.     

The biological effect of polyamines on heart RNA and histone metabolism

Summary We have observed a close relationship between polyamines (spermine and spermidine) and nucleic acids in connection with myocardial hypertrophy obtained by aortic constriction or by physical exercise. The role of spermine in RNA synthesis has been investigated on perfused heart, and we have observed a rapid increase of ribose-5-³H incorporation into RNA subcellular fractions. With the same experimental conditions we have considered the action of spermine on histone acetylation. The arginine-rich fractions are more acetylated under the action of spermine. This finding indicates a positive action of spermine on gene derepression mechanism.An invited article.     

The effect of light stimulation in the pre- and postnatal periods on the synaptic ultrastructure in the chick hyperstriatum

Morphometric analysis of synapses in the medial parts of the ventral and accessorium hyperstriatum in the right and left hemispheres in chicks has been performed after rhythmic optic stimulation from the 18th day of incubation, flickering stimulation at the 11-12th hour after hatching, as well as in chicks reared under normal illumination and those kept in darkness within the first two days after hatching. Numeric density of synapses, mean dimensions of postsynaptic thickenings, the number of synaptic vesicles per active zone in presynapses and mean length of the whole axodendritic contact were determined in ultrathin sections. The data obtained indicate that early visual experience significantly affects the synaptic structures in both parts of the brain. A discussion is made of the plasticity of synapses during stimulation, morphological and functional relationships between hyperstriatal areas in relation to different aspects of processing and storage of visual information.     

Interferon-mediated effect on ribosomal RNA metabolism

Ribosomal RNA (rRNA) has been shown to be involved in the binding of bacterial messenger RNA (mRNA) and an analogous 18 S rRNA · mRNA complex has been reported in eukaryotic systems. Thus, qualitative changes in host rRNA may be involved in the development of the interferon mediated antiviral state, a process thought to involve the inability of host ribosomes to bind and recognize viral mRNA. Data are reported which suggest that trisomy 21 human fibroblasts respond to human interferon with a marked reduction in cytoplasmic rRNA. [³H]Uridine was used to radioactively label the polysomal RNAs for 24 h beginning 12 h after interferon addition. Subsequent sucrose gradient analysis of the phenol or SDS-extracted RNA revealed that the reduction in radioactive rRNA was nearly complete for the 28 S rRNA. In contrast, considerable residual uridine incorporation was found in the 18 S rRNA species. Corollary data suggesting a net increase in mRNA synthesis and a net decrease in protein synthesis are reported.     

Relationships between the effect of O2 on energy metabolism and RNA synthesis in Rhodotorula gracilis

In the aerobic yeast Rhodotorula gracilis, a decrease in O₂availability, from saturating conditions (pO₂ = 100 mm Hg) topO₂ = 1 mm Hg, causes a decrease in the growth rate accompaniedby a fall in the accumulation rate of RNA and, to a lesser extent,of proteins. At pO₂ = 1, no relevant changes in the levels oftriphosphate nucleotides (ATP, GTP, CTP and UTP) are observedwith respect to the controls, while the ADP and AMP levels markedlyincrease. The uptake of labelled precursors and qualitative analysis ofRNA suggest that the decrease in the RNA accumulation rate atpO₂ = 1 is due to a decreased RNA synthesis rate. This paper examines the mechanism by which low availabilityof O₂ causes a decrease in the RNA synthesis rate even thoughtotal triphosphate nucleotide levels remain high. (Received December 28, 1977; )     

Cyclic Adenosine Monophosphate in the Nervous System of Aplysia californica : I. Increased synthesis in response to synaptic stimulation

In the isolated abdominal ganglion of Aplysia, previously incubated in adenine-³H, the amount of ³H-labeled adenosine-3',5' monophosphate (cAMP) doubled after electrical stimulation of nerves at a physiological rate (1/sec). No change was detected after 4 min of stimulation. An increase in cAMP was first seen after 15 min; lengthening the period of stimulation to 1 hr did not increase the extent of the effect. ATP contained 50% of the total radioactivity taken up from adenine-³H, cAMP about 0.1%. During stimulation both the total amount and the specific radioactivity of adenosine triphosphate (ATP) did not change. Thus, the increased amount of radioactivity found in cAMP after stimulation represented an increase in its rate of synthesis. During stimulation formation of cAMP-³H was not altered in nerves or in the cell body of an identified neuron (R2). In addition, no changes were detected in the total amounts of cAMP in the ganglion and in the cell body of R2. It seems likely that the increase was initiated by synaptic activity rather than by action potentials. It was blocked by elevating the concentration of Mg, which also blocks synaptic activity without impairing conduction of impulses. Moreover, impulse activity induced by ouabain and glutamate did not result in increased formation of cAMP.