Fetal Patterns of Interlimb Movement Synchrony, Facial Wiping, and Nipple Attachment are Altered by Prenatal Exposure to Methylazoxymethanol (MAM)

There is considerable interest in the early detection of neuromotor deficits, including disorders that may be the result of toxin exposure during early development. Until recently, quantifiable methods for determining the immediate developmental effects of prenatal toxin exposure have been unavailable. However, several behavioral measures employed in this lab have shown clear prenatal patterns of development, suggesting their possible utility in detecting early assaults to the CNS. To test this hypothesis, pregnant rats were injected with the neurotoxin methyazoxymethanol (MAM, Midwest Research Inst.) on E17 of gestation. Fetuses then were prepared for in vivo behavioral observation 72 hours later, on E20, to measure: (a) interlimb movement synchrony between different pairwise limb combinations during spontaneous movement, (b) facial wiping response to intraoral lemon infusion, which requires coordination between forepaws and face, and (c) presentation of an artificial nipple, which evokes oral grasping responses in fetal rats. Although MAM-treated subjects did not differ from saline controls in overall appearance and weight, clear disruptions of movement coordination were seen in all three behavioral measures. These results suggest that these quantifiable behavioral measures may be useful in the prenatal assessment of CNS deficits. Supported by grant HD 33862 to SRR

Prenatal Methylazoxymethanol Exposure alters Evoked Responses in Fetal Rats

Although there is considerable interest in identifying methods to detect central nervous system impairment early in development, few behavioral assessment tools are available for detecting CNS deficits in the fetus. In the present study, methylazoxymethanol [MAM; Midwest Research Institute, (MRI)] was used to induce deficits in CNS development in fetal rats to assess effects on coordinated fetal behavior. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via intraperitoneal injection and then were prepared for behavioral testing 3 days later on E20. After externalization from the uterus into a warm saline bath, fetal subjects received either an intraoral infusion of lemon extract to evoke a facial wiping response or were presented with an artificial nipple to evoke an oral grasping response. Interlimb coordination and paw–face contact during facial wiping were disrupted in MAM-exposed fetuses. Similarly, MAM exposure diminished the ability of fetuses to grasp or maintain oral contact with the artificial nipple. Although clear disruptions of movement coordination were seen in the MAM-treated subjects, there were no significant differences from saline controls in weight or anatomical measures. Together, these findings suggest that behavioral assessments of fetal motor coordination may be useful in identifying neural insult during prenatal development

Prenatal Exposure to Methylazoxymethanol (MAM) Alters Patterns of Interlimb Movement Synchrony in Fetal Rats

It has long been suspected that early exposure to toxins may contribute to the development of some neurological disorders (e.g. ALS, cerebral palsy, and Parkinson\u27s Disease). Although methods associating early exposure and neurological outcome are widely available, methods for determining the immediate developmental effects of exposure have, until recently, been unavailable. Previous work with fetal behavior in this lab has shown that quantification of spontaneous movement reveals clear patterns across development. One such measure, interlimb synchrony, quantifies the temporal relationship of movements between pairwise combinations of limbs. The aim of this study was to assess whether arrested neural development, induced by exposure to the neurotoxin methylazoxymethanol (MAM, Midwest Research Institute), would be evident in the organization of spontaneous motor activity in fetal rats. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via IP injection and were then prepared for in vivo behavioral observation on E20. Motor activity was quantified during playback of videotape records. Overall results showed no differences in litter size or fetal weight between the treatment groups and saline controls. However, alterations in patterns of synchrony involving the hindlimbs were seen in treated subjects. These findings of behavioral deficits in fetal subjects exposed to MAM, which appear otherwise normal, suggest that direct measures of fetal behavior, such as interlimb synchrony, may be useful in the early diagnosis of developmental disorders of the nervous system

Prenatal methylazoxymethanol exposure alters evoked responses in fetal rats

Abstract Although there is considerable interest in identifying methods to detect central nervous system impairment early in development, few behavioral assessment tools are available for detecting CNS deficits in the fetus. In the present study, methylazoxymethanol [MAM; Midwest Research Institute, (MRI)] was used to induce deficits in CNS development in fetal rats to assess effects on coordinated fetal behavior. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via intraperitoneal injection and then were prepared for behavioral testing 3 days later on E20. After externalization from the uterus into a warm saline bath, fetal subjects received either an intraoral infusion of lemon extract to evoke a facial wiping response or were presented with an artificial nipple to evoke an oral grasping response. Interlimb coordination and paw -face contact during facial wiping were disrupted in MAM-exposed fetuses. Similarly, MAM exposure diminished the ability of fetuses to grasp or maintain oral contact with the artificial nipple. Although clear disruptions of movement coordination were seen in the MAM-treated subjects, there were no significant differences from saline controls in weight or anatomical measures. Together, these findings suggest that behavioral assessments of fetal motor coordination may be useful in identifying neural insult during prenatal development

Utility of Fetal Movement Coordination in Assessing Nervous System Functioning after Prenatal Administration of the Neurotoxin Methylazoxymethanol (MAM)

It is now thought that some neuromotor disorders (e.g., cerebral palsy, ALS, Parkinson disease) may be the result of toxin exposure early in development. Consequently, methods to assess impairments in early nervous system functioning are of considerable interest to both researchers and clinicians. While such methods already have been developed for the postnatal period, few tools exist for the assessment of fetal nervous system functioning. Behavioral measures used in our lab have shown clear developmental patterns, suggesting they may be useful in detecting early assaults to the central nervous system. To test this hypothesis, pregnant rats were given an injection of the neurotoxin methylazoxymethanol (MAM) on E17 of gestation. On E20, 72 hours later, fetuses were prepared for in vivo testing, which consisted of the following behavioral observations: (a) spontaneous movement, (b) facial wiping in response to lemon infusion, and (c) response to an artificial nipple presentation. Quantification of these three measures showed clear disruptions of movement coordination in the MAM-treated subjects, with no discernable differences from saline controls in weight or anatomical measures. These findings suggest that prenatal behavioral assessments of motor coordination, either spontaneous or evoked, may be useful in identifying neural insult during fetal development

Prenatal Methylazoxymethanol Exposure alters Evoked Responses in Fetal Rats

Although there is considerable interest in identifying methods to detect central nervous system impairment early in development, few behavioral assessment tools are available for detecting CNS deficits in the fetus. In the present study, methylazoxymethanol [MAM; Midwest Research Institute, (MRI)] was used to induce deficits in CNS development in fetal rats to assess effects on coordinated fetal behavior. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via intraperitoneal injection and then were prepared for behavioral testing 3 days later on E20. After externalization from the uterus into a warm saline bath, fetal subjects received either an intraoral infusion of lemon extract to evoke a facial wiping response or were presented with an artificial nipple to evoke an oral grasping response. Interlimb coordination and paw–face contact during facial wiping were disrupted in MAM-exposed fetuses. Similarly, MAM exposure diminished the ability of fetuses to grasp or maintain oral contact with the artificial nipple. Although clear disruptions of movement coordination were seen in the MAM-treated subjects, there were no significant differences from saline controls in weight or anatomical measures. Together, these findings suggest that behavioral assessments of fetal motor coordination may be useful in identifying neural insult during prenatal development

Prenatal Exposure to Methylazoxymethanol (MAM) Alters Patterns of Interlimb Movement Synchrony in Fetal Rats

It has long been suspected that early exposure to toxins may contribute to the development of some neurological disorders (e.g. ALS, cerebral palsy, and Parkinson\u27s Disease). Although methods associating early exposure and neurological outcome are widely available, methods for determining the immediate developmental effects of exposure have, until recently, been unavailable. Previous work with fetal behavior in this lab has shown that quantification of spontaneous movement reveals clear patterns across development. One such measure, interlimb synchrony, quantifies the temporal relationship of movements between pairwise combinations of limbs. The aim of this study was to assess whether arrested neural development, induced by exposure to the neurotoxin methylazoxymethanol (MAM, Midwest Research Institute), would be evident in the organization of spontaneous motor activity in fetal rats. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via IP injection and were then prepared for in vivo behavioral observation on E20. Motor activity was quantified during playback of videotape records. Overall results showed no differences in litter size or fetal weight between the treatment groups and saline controls. However, alterations in patterns of synchrony involving the hindlimbs were seen in treated subjects. These findings of behavioral deficits in fetal subjects exposed to MAM, which appear otherwise normal, suggest that direct measures of fetal behavior, such as interlimb synchrony, may be useful in the early diagnosis of developmental disorders of the nervous system

Utility of Fetal Movement Coordination in Assessing Nervous System Functioning after Prenatal Administration of the Neurotoxin Methylazoxymethanol (MAM)

It is now thought that some neuromotor disorders (e.g., cerebral palsy, ALS, Parkinson disease) may be the result of toxin exposure early in development. Consequently, methods to assess impairments in early nervous system functioning are of considerable interest to both researchers and clinicians. While such methods already have been developed for the postnatal period, few tools exist for the assessment of fetal nervous system functioning. Behavioral measures used in our lab have shown clear developmental patterns, suggesting they may be useful in detecting early assaults to the central nervous system. To test this hypothesis, pregnant rats were given an injection of the neurotoxin methylazoxymethanol (MAM) on E17 of gestation. On E20, 72 hours later, fetuses were prepared for in vivo testing, which consisted of the following behavioral observations: (a) spontaneous movement, (b) facial wiping in response to lemon infusion, and (c) response to an artificial nipple presentation. Quantification of these three measures showed clear disruptions of movement coordination in the MAM-treated subjects, with no discernable differences from saline controls in weight or anatomical measures. These findings suggest that prenatal behavioral assessments of motor coordination, either spontaneous or evoked, may be useful in identifying neural insult during fetal development

Fetal Patterns of Interlimb Movement Synchrony, Facial Wiping, and Nipple Attachment are Altered by Prenatal Exposure to Methylazoxymethanol (MAM)

There is considerable interest in the early detection of neuromotor deficits, including disorders that may be the result of toxin exposure during early development. Until recently, quantifiable methods for determining the immediate developmental effects of prenatal toxin exposure have been unavailable. However, several behavioral measures employed in this lab have shown clear prenatal patterns of development, suggesting their possible utility in detecting early assaults to the CNS. To test this hypothesis, pregnant rats were injected with the neurotoxin methyazoxymethanol (MAM, Midwest Research Inst.) on E17 of gestation. Fetuses then were prepared for in vivo behavioral observation 72 hours later, on E20, to measure: (a) interlimb movement synchrony between different pairwise limb combinations during spontaneous movement, (b) facial wiping response to intraoral lemon infusion, which requires coordination between forepaws and face, and (c) presentation of an artificial nipple, which evokes oral grasping responses in fetal rats. Although MAM-treated subjects did not differ from saline controls in overall appearance and weight, clear disruptions of movement coordination were seen in all three behavioral measures. These results suggest that these quantifiable behavioral measures may be useful in the prenatal assessment of CNS deficits. Supported by grant HD 33862 to SRR

Prenatal Exposure to Methylazoxymethanol (MAM) Alters Coordination in Facial Wiping and Oral Grasping Responses of Fetal Rats

One of the sequelae of neurodevelopmental disorders such as cerebral palsy is impaired movement coordination. There is considerable clinical interest in identifying diagnostic methods to detect such disorders early in development, when therapies may be more effective. However, few assessment tools are available for detecting CNS deficits in the fetus. In the present study, methylazoxymethanol (MAM, Midwest Research Institute) was used to induce deficits in CNS development in fetal rats to assess effects on coordinated fetal behavior. Fetuses were exposed by administering MAM to pregnant rats on E17 of gestation via IP injection and were then prepared for behavioral testing 3 days later on E20. After externalization from the uterus into a warm saline bath, fetal subjects were secured in a supine posture for observation. The first subject received an intraoral infusion of lemon extract to evoke a facial wiping response, which involves coordination of both forepaws in contact with the face. The second subject was presented with an artificial nipple to evoke oral grasping responses. Both MAM-treated fetuses and saline controls were responsive to both stimuli. However, interlimb coordination and paw-face contact during facial wiping were disrupted in MAM-exposed fetuses. Similarly, MAM exposure diminished the ability of fetuses to grasp or maintain oral contact with the artificial nipple. These findings suggest that behavioral assessments of motor coordination during stimulus-evoked action patterns may be useful in identifying neural insult during prenatal development