Neuroteratology and Animal Modeling of Brain Disorders.

Over the past 60 years, a large number of selective neurotoxins were discovered and developed, making it possible to animal-model a broad range of human neuropsychiatric and neurodevelopmental disorders. In this paper, we highlight those neurotoxins that are most commonly used as neuroteratologic agents, to either produce lifelong destruction of neurons of a particular phenotype, or a group of neurons linked by a specific class of transporter proteins (i.e., dopamine transporter) or body of receptors for a specific neurotransmitter (i.e., NMDA class of glutamate receptors). Actions of a range of neurotoxins are described: 6-hydroxydopamine (6-OHDA), 6-hydroxydopa, DSP-4, MPTP, methamphetamine, IgG-saporin, domoate, NMDA receptor antagonists, and valproate. Their neuroteratologic features are outlined, as well as those of nerve growth factor, epidermal growth factor, and that of stress. The value of each of these neurotoxins in animal modeling of human neurologic, neurodegenerative, and neuropsychiatric disorders is discussed in terms of the respective value as well as limitations of the derived animal model. Neuroteratologic agents have proven to be of immense importance for understanding how associated neural systems in human neural disorders may be better targeted by new therapeutic agents.

Active maternal phenotype is established before breeding and leads offspring to align growth trajectory outcomes and reflex ontogeny.

The main goals of this study were to classify dams according to the level of voluntary physical activity before breeding and during pregnancy/lactation and to evaluate the effects on growth trajectory and reflex ontogenesis of offspring. Voluntary physical activity was ranked by traveled distance, time and daily estimated calorie burned. Thirty-five female Wistar rats were classified as control (C, n=5), inactive (I, n=10), active (A, n=8) and very active (VA, n=12). During 30d before breeding, traveled distance, average speed, time and calorie burned were daily recorded for active and very active groups. Traveled distance was recorded each 2h every day of adaptation. Body weight, food intake and fasting glycemia were measured throughout the experiment. During lactation, litters were evaluated in terms of physical features and reflex ontogeny. VA showed a progressive increase in the traveled distance and time while A dams presented constant values. VA rats showed lower body weight and higher food intake. During pregnancy, both groups performed less than 1km/day. Pups from A and VA dams showed higher lateral-lateral axis of the skull, longitudinal axis, tail length, and anticipation of the pavilion and auditory canal opening, and erupting incisors. I, A and VA groups showed a delay of righting, cliff aversion and vibrissae placing reflexes. In conclusion, active maternal phenotype is established before breeding allowing mothers to fit ecological and influencing growth trajectory outcomes and reflex ontogeny of the offspring based on matrilineal experience.