Teratology, “Double Hit” Hypothesis, and the Concept Fetal Mal-Programming
The third trimester of pregnancy (i.e., the prenatal period) and the first few years of life are crucial for brain development (Yang et al., 2011). During the early developmental stages in laboratory animals and humans, the ECSS is present in the CNS and plays a critical role in neuronal development and organization (Calvigioni et al., 2014). During the critical third trimester, the brain develops rapidly through the following sequential and interdependent processes: neurogenesis, axonal and dendritic growth, synaptogenesis, cell death, synaptic pruning, myelination, and gliogenesis (Yang et al., 2011). Intuitively, exogenous cannabinoid use during the critical stages …show more content…
First, the vulnerability range of the CNS to a specific neuroteratogen is from the fetal stage through infancy, including all critical periods of CNS development (e.g., neurogenesis, neuronal differentiation, arborization, synaptogenesis, functional synaptic organization, myelination, gliogenesis, glial migration, differentiation, and organogenesis), and depends on the genotypes of the maternal/fetus dyad and their response to environmental factors. Second, the most common manifestations of injury to the developing CNS, in general, and, perhaps, to the ECSS, in particular, do not result in overt nervous system malformations (i.e., a specific neurodevelopmental phenotype, as seen in Fetal alcohol spectrum disorder), but result in covert functional abnormalities. These covert abnormalities are undetectable at birth but may be manifested after a “second hit” (i.e., The “Double Hit” Hypothesis; that is, the organism must “grow into its deficit” via trauma and/or stress). The “first hit” landed by intrauterine cannabis exposure (ICE) may cause only subtle “buckling” of the developing nervous system, perhaps, due to perturbation of the ECSS. The “second hit” is the power punch, which “cripples” the developing nervous system, and is manifested …show more content…
2011; Campolongo et al. 2009; Fried 2002; Fried and Smith 2001; Huizink and Mulder 2006; Navarro et al. 1995; Schneider 2009; Trezza et al. 2008b). A neuroteratogen can be defined as any medicinal or recreational drug that acts during embryonic or fetal development to produce permanent structural and functional abnormalities (i.e., fetal developmental mal-programming). The fetal programming hypothesis states that several organ structures and functions will be programmed via in utero presentation of external stimuli to the fetus (i.e., maternal programming), which will determine the set points of physiological and metabolic responses that will continue into adulthood (Calvigioni et al., 2014; Lau et al., 2011). For example, over the last twenty years, it has been recognized that the risk of obesity and metabolic syndrome can be influenced by prenatal and neonatal growth trajectories, and environmental exposures (Lau et al., 2011). This fetal mal-programming hypothesis has been expanded to include the effect of early childhood development on a variety of adult disorders (Lau et al., 2011). Maternal programming is a major contributor
The third trimester of pregnancy (i.e., the prenatal period) and the first few years of life are crucial for brain development (Yang et al., 2011). During the early developmental stages in laboratory animals and humans, the ECSS is present in the CNS and plays a critical role in neuronal development and organization (Calvigioni et al., 2014). During the critical third trimester, the brain develops rapidly through the following sequential and interdependent processes: neurogenesis, axonal and dendritic growth, synaptogenesis, cell death, synaptic pruning, myelination, and gliogenesis (Yang et al., 2011). Intuitively, exogenous cannabinoid use during the critical stages …show more content…
First, the vulnerability range of the CNS to a specific neuroteratogen is from the fetal stage through infancy, including all critical periods of CNS development (e.g., neurogenesis, neuronal differentiation, arborization, synaptogenesis, functional synaptic organization, myelination, gliogenesis, glial migration, differentiation, and organogenesis), and depends on the genotypes of the maternal/fetus dyad and their response to environmental factors. Second, the most common manifestations of injury to the developing CNS, in general, and, perhaps, to the ECSS, in particular, do not result in overt nervous system malformations (i.e., a specific neurodevelopmental phenotype, as seen in Fetal alcohol spectrum disorder), but result in covert functional abnormalities. These covert abnormalities are undetectable at birth but may be manifested after a “second hit” (i.e., The “Double Hit” Hypothesis; that is, the organism must “grow into its deficit” via trauma and/or stress). The “first hit” landed by intrauterine cannabis exposure (ICE) may cause only subtle “buckling” of the developing nervous system, perhaps, due to perturbation of the ECSS. The “second hit” is the power punch, which “cripples” the developing nervous system, and is manifested …show more content…
2011; Campolongo et al. 2009; Fried 2002; Fried and Smith 2001; Huizink and Mulder 2006; Navarro et al. 1995; Schneider 2009; Trezza et al. 2008b). A neuroteratogen can be defined as any medicinal or recreational drug that acts during embryonic or fetal development to produce permanent structural and functional abnormalities (i.e., fetal developmental mal-programming). The fetal programming hypothesis states that several organ structures and functions will be programmed via in utero presentation of external stimuli to the fetus (i.e., maternal programming), which will determine the set points of physiological and metabolic responses that will continue into adulthood (Calvigioni et al., 2014; Lau et al., 2011). For example, over the last twenty years, it has been recognized that the risk of obesity and metabolic syndrome can be influenced by prenatal and neonatal growth trajectories, and environmental exposures (Lau et al., 2011). This fetal mal-programming hypothesis has been expanded to include the effect of early childhood development on a variety of adult disorders (Lau et al., 2011). Maternal programming is a major contributor