Ascertaining in the mouse and chick models the mechanisms of neural and behavioral birth defects induced by various agents, mainly organophosphates and heroin, and their reversal with mesenchymal and neural stem cell (MSC, NSC) therapies; understanding the mechanisms by which the transplanted cells exert their therapeutic action.
Currently, we are similarly working towards understanding neurobehavioral birth defects induced by parental (paternal and/or maternal-preconception) exposure. Most probably via the epigenetic genomic imprinting mechanisms. Again, with reversing the deficits with stem cell transplantation.
In the mouse model, the study of the mechanisms focuses on behaviors related to the septohippocampal cholinergic innervation (Morris and eight-arm mazes). Our hypothesis is that abolishment in the hippocampus of cholinergic receptor-induced translocation/activation of PKCγ represents a principal component in the mechanism by which various substances induces neurobehavioral birth defects.
Our parallel chick model, which controls for maternal confounds, involves perturbation by the teratogen of imprinting related to defects where the mechanism is again abolishment of translocation/activation of PKCγ in the IMHV (IMM) nucleus.
In both models we are promoting the novel hypothesis that one major mechanism by which stem cells exert their therapeutic action is by inducing neurogenesis, i.e. proliferation of endogenous precursors.
In both models the changes in synaptic function may be regulated by the teratogen- induced epigenetic alterations.
Research milestones old and new:
• Being one of the founders of the modern Behavioral Teratology, thus expanded the concept by introducing the study of the mechanisms of the defects termed “Neurobehavioral Teratology” (Yanai 1984, Yaniv et al 2004).
• Developing the model for the reversal of neurobehavioral teratogenicity, in mice, by way of neural grafting (Steingart et al 2000, Yanai & Pick 1988).
• Reversal of neurobehavioral teratogenicity in mice by manipulations of the A10 regulating neural pathways (Yanai et al 1987, Yanai et al 1989).
• Reversal of neurobehavioral teratogenicity, in mice, via nicotine therapy (Beer et al 2005).
• Reversal of neurobehavioral teratogenicity, in mice, via transplantation of various types of stem cells (Ben-Shaanan et al 2008, Izrael et al 2004, Katz et al 2008, Turgeman et al 2011, Yanai et al 2005, Yanai et al 1995a).
• The establishment of models for the reversal of neurobehavioral deficits in the avian: a. Parkinson’s disease in the adult chicken (Yanai et al 1995b), b. reversal of neurobehavioral teratogenicity in a chick embryo model (Pinkas et al 2013).
• Establishing the principle that one major mechanism by which stem cells exert their therapeutic effect is the induction of neurogenesis (Ben-Shaanan et al 2008, Pinkas et al 2013).