Yuri B. Shmukler

From oocyte to neuron: Do neurotransmitters function in the same way throughout development?

Summary1.Classical neurotransmitters (such as acetylcholine, biogenic amines, and GABA) are functionally active througout ontogenesis.2.Based on accumulated evidence, reviewed herein, we present an hypothetical scheme describing developmental changes in this functional activity, from the stage of maturing oocytes through neuronal differentiation. This scheme reflects not only the spatio-temporal sequence of these changes, but also the genesis of neurotransmitter functions, from “protosynapses” in oocytes and cleaving embryos to the development of functional neuronal synapses.3.Thus, it appears that neurotransmitters participate in various forms of intra- and intercellular signalling throughout all stages of ontogenesis.

Serotonergic-induced ion currents in cleaving sea urchin embryos

Summary Using the whole-cell voltage clamp technique on early sea urchin embryos at different stages of the cell cycle, we showed that agonists of 5-HT receptor subtypes induce inward currents. The current induced by 5-HT3 receptor agonists is dose dependent and reverses between −25 and +15 mV suggesting, it is carried by nonspecific ion channels. 5-HT3 receptor agonists showed more pronounced effects when administered during cleavage furrow formation. The effects are accompanied by the increase of steady-state conductance and calcium current activity. These results suggest that serotonergics and ion channel activity play a role in the regulation of cellular events during cleavage division in the early sea urchin embryo, supporting the idea of a proto-synapse between blastomeres.

Expression of serotonergic system components during early Xenopus embryogenesis

Despite abundant research studies on the physiological and biochemical nature of embryonic neurotransmitter function, little is known about the molecular genetic mechanisms involved. The expression of the main components of the serotonergic system during early Xenopus embryogenesis was investigated using RT-PCR, real time PCR and in situ hybridization. Transcripts encoding the serotonin receptors HTR2C and HTR7, as well as the vesicular monoamine transporter VMAT2, the serotonin transporter (SERT) and the serotonin synthesis enzymes tryptophan hydroxylase (TPH2) and aromatic amino acid decarboxylase (AAAD) were found to be expressed during the cleavage division stages, whereas the degradation enzyme monoamine oxidase A (MAOA) was absent. The main components of the serotonergic system were found to be expressed during the earliest stages of embryonic development. The embryonic transmitter mechanism, its complexity, and its variability among various species are discussed.

Ladder-shaped ion channel ligands: Current state of knowledge

Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of Gambierdiscus and Karenia genera, correspondingly. Ciguatera, evoked by CTXs, is a type of ichthyosarcotoxism, which involves a variety of gastrointestinal and neurological symptoms, while BTXs cause so-called neurotoxic shellfish poisoning. Both types of toxins are reviewed together because of similar mechanisms of their action. These are the only molecules known to activate voltage-sensitive Na+-channels in mammals through a specific interaction with site 5 of its α-subunit and may compete for it, which results in an increase in neuronal excitability, neurotransmitter release and impairment of synaptic vesicle recycling. Most marine ciguatoxins potentiate Nav channels, but a considerable number of them, such as gambierol and maitotoxin, have been shown to affect another ion channel. Although the extrinsic function of these toxins is probably associated with the function of a feeding deterrent, it was suggested that their intrinsic function is coupled with the regulation of photosynthesis via light-harvesting complex II and thioredoxin. Antagonistic effects of BTXs and brevenal may provide evidence of their participation as positive and negative regulators of this mechanism.

Transmitters in Blastomere Interactions

Normal multicellular organism develops from fertilized egg cell, although the latter may give birth for twins too. Mechanisms that lead to the realization of these variants of the development may differ greatly, however, it naturally suggests itself that such deviation as twin formation is conditioned by this or that disturbance of cellular interactions. But the very fact of the existence of such interactions after classic experiments remained disputable until now. Naturally, far less is known on the suggested mechanisms of such interactions that provide the formation of integral organism or, correspondingly, their distortion that lead to the twins formation.

Expression and functional activity of neurotransmitter system components in sea urchins’ early development

Reverse-transcription polymerase chain reaction (RT-PCR) investigation of the expression of the components supposedly taking part in serotonin regulation of the early development of Paracentrotus lividus has shown the presence of transcripts of five receptors, one of which has conservative amino acid residues characteristic of monoaminergic receptors. At the early stages of embryogenesis the expressions of serotonin transporter (SERT) and noradrenaline transporter (NET) were also recognized. The activities of the enzymes of serotonin synthesis and serotonin transporter were shown using immunohistochemistry and incubation with para-chlorophenylalanine (PСРА) and 5-hydroxytryptophan (HTP). Pharmacological experiments have shown a preferential cytostatic activity of ligands characterized as mammalian 5-hydroxytryptamine (5-HT)1-antagonists. On the basis of the sum of the data from molecular biology and embryo physiological experiments, it is suggested that metabotropic serotonin receptors and membrane transporters take part in the regulatory processes of early sea urchin embryogenesis.

Gennady A. Buznikov, PhD (1931-2012): Father of Neurotransmitters as Developmental Signals

thesis, which he successfully defended in 1956. However, this work did not become the main direction of Gennady’s research. The events that determined the direction of his research career occurred at the end of the 1950s, when he, together with his colleague Boris Manukhin, followed up on the proposal by Koshtoyantz that chemical mechanisms of the nervous system are derived from the prenervous system of regulation in early development. In 1961, they published the first evidence that 5-hydroxytryptamine (5-HT) regulated embryogenesis in a marine molGennady Buznikov died on August 27, 2012, in Los Angeles, Calif., USA, where he lived with his wife Lyuda Nikitina, after a brief illness (fig. 1). He was born on January 18, 1931, in Leningrad (Saint Petersburg), Russia. His early childhood left a lasting impression. Before World War II, his father was subjected to political repression and imprisoned. When Gennady was only 10, he was evacuated from Leningrad just before the city was sieged by the Germans in 1941, and placed in a children’s home. Despite this, Gennady had the strength of character and natural abilities to pass the entrance exam for admission to the Biology Faculty of the M.V. Lomonosov Moscow State University, where he pursued his graduate studies. The post-war wave of political repressions caused his mother to lose her job and be blacklisted. This left the family penniless, except for a small scholarship and parttime work of Gennady. Life obstacles were balanced to some extent by success in scientific research in the Department of Human and Animal Physiology at Moscow State University, carried out under the direction of Prof. Khachatur Koshtoyantz. This research on the role of hyaluronidases in the hatching of bony fish began as a student research project and became the basis of his PhD Received: July 4, 2013 Accepted: July 4, 2013 Published online: September 28, 2013