Critical periods for behavioral anomalies in mice.

Abstract

hile mice have been used less frequently than rats in behavioral research, their use has some advantages in teratological studies. The development of the mouse CNS has been investigated more extensively than that of the rat. Since time of insult has been found to be an important factor in effects on both anatomy and behavior, data on the sequence of events in CNS development are valuable in planning and interpreting behavioral assessments of potential teratogens. A comparison of studies in mice and rats suggests that behavioral effects of teratogens are similar in the two species and demonstrates that mice can be used successfully in a variety of behavioral evaluations.The traditional use of mice in embryology has provided data that make the species desirable for teratological studies. When the teratological assessment involves behavior, however, many investigators perfer rats, mainly because there is such a wealth of behavioral data available for the second species. Rats do tend to be more vigorous, easier to train, and much easier to handle. The latter qualities can be important to the experimenter in studies where animals receive many trials, but such differences do not prohibit the use of mice, they only serve to explain why rats have been used more often. The thesis of this paper is that mice should not be considered poor subjects for behavioral studies. In fact, there are enough data available to indicate that teratogenic effects on behavior are quite similar in the two species.For those interested in correlating behavioral deficits with alterations of the CNS, mice present one special advantage: the development of the mouse CNS has been studied more extensively than that of the rat. The idea that there are critical periods in development for the production of particular abnormalities is hardly new. Wilson (1) has described periods of peak sensitivity for several systems. The stages when interference

Effects of Environmentally Relevant Mixtures of Persistent Organic Pollutants on the Developmental Neurobiology in Rats

“…It is unclear whether the prenatal exposure to these mixtures has been linked to reduced fetal and postnatal growth, neurological deficits, delayed development of motor functions, and impaired short-term memory (Kodavanti 2005;Seegal 2000;Seegal, Pappas, and Park 1998). The developmental processes, including neurogenesis, migration, synaptogenesis, gliogenesis, and myelination, are extremely susceptible to damage from exposure to environmental insult (Garman et al 2001;Tilson 2000;Rodier, Reynolds, and Roberts 1979;Rodier 1976). These sequences of events are genetically programmed and interference at any stage may alter subsequent development and result in permanent impairment.…”

“…These sequences of events are genetically programmed and interference at any stage may alter subsequent development and result in permanent impairment. In adults, they have generally reached a steady state and are not potential targets for neurotoxic agents (Garman et al 2001;Tilson 2000;Campbell et al 1997;Rodier, Reynolds, and Roberts 1979;Rodier 1976). Extensive studies using lead, mercury, methylazoxymethanol, alcohol, methylmercury, nicotine, and chlorpyrifos have shown that these chemicals affect multiple pathways during normal development (Erickson and Talts 2000;Campbell et al 1997;Chanda and Pope 1996).…”

Developmental neurotoxicology of endocrine disruptors and pesticides: identification of information gaps and research needs.

“…Chemicalinduced neurodevelopmental effects could depend on variables such as changes in environmental temperature, hormonal status, and life-cycle stage. Neurotoxicity following developmental exposure to chemicals can vary qualitatively and quantitatively depending on the phase of nervous system maturation (4,5). Thus, a chemical could affect neurodevelopmental processes if exposure occurred during a critical period of neuroendocrine maturation, but have little or no effect if exposure occurred at some other period of development.…”

“…Neurogenesis, migration, synaptogenesis, gliogenesis, and myelination are developmental processes that have generally reached a steady state in the adult and are not potential targets for neurotoxic agents. There are several examples in the literature demonstrating that exposure to a chemical during a critical period of development will produce neurotoxicity, whereas exposure to the same chemical during adulthood will have little or no effect (4)(5)(6).…”

Research strategies for behavioral teratology studies.

“…This reflects the rapid proliferation of neural tissue during early development and the establishment of functional synaptic contacts as the brain matures. In regard to the former process, i.e., cell proliferation, data on actual periods of maximum proliferation of neurons comprising different regions in the brain of the rat and mouse are summarized in this session's paper by Rodier (12) and indicate that neural proliferation in some brain areas continues for some time after birth. As the proliferation process ends, however, functional brain capacity probably begins to reach as asymptote, likely sometime not long after puberty, and is seen in the present scheme as leveling off for a prolonged period during adulthood.…”