Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.

Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed. A previous study has found that VPA treatment strongly reduces δ-catenin mRNA levels in cultured human neurons. δ-catenin is important for the control of glutamatergic synapses and is strongly associated with ASD. VPA inhibits dendritic morphogenesis in developing neurons, an effect that is also found in neurons lacking δ-catenin expression. We thus hypothesize that prenatal exposure to VPA significantly reduces δ-catenin levels in the brain, which impairs glutamatergic synapses to cause ASD. Here, we found that prenatal exposure to VPA markedly reduced δ-catenin levels in the brain of mouse pups. VPA treatment also impaired dendritic branching in developing mouse cortical neurons, which was partially reversed by elevating δ-catenin expression. Prenatal VPA exposure significantly reduced synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor levels and postsynaptic density 95 (PSD95) in the brain of mouse pups, indicating dysfunctions in glutamatergic synaptic transmission. VPA exposure also significantly altered ultrasonic vocalization (USV) in newly born pups when they were isolated from their nest. Moreover, VPA-exposed pups show impaired hypothalamic response to isolation, which is required to produce animals' USVs following isolation from the nest. Therefore, these results suggest that VPA-induced ASD pathology can be mediated by the loss of δ-catenin functions.

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.

Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed. A previous study has found that VPA treatment strongly reduces δ-catenin mRNA levels in cultured human neurons. δ-catenin is important for the control of glutamatergic synapses and is strongly associated with ASD. VPA inhibits dendritic morphogenesis in developing neurons, an effect that is also found in neurons lacking δ-catenin expression. We thus hypothesize that prenatal exposure to VPA significantly reduces δ-catenin levels in the brain, which impairs glutamatergic synapses to cause ASD. Here, we found that prenatal exposure to VPA markedly reduced δ-catenin levels in the brain of mouse pups. VPA treatment also impaired dendritic branching in developing mouse cortical neurons, which was reversed by elevating δ-catenin expression. Prenatal VPA exposure significantly reduced synaptic AMPA receptor levels and postsynaptic density 95 (PSD95) in the brain of mouse pups, indicating dysfunctions in glutamatergic synaptic transmission. VPA exposure also significantly altered ultrasonic vocalization (USV) in newly born pups when they were isolated from their nest. Moreover, VPA-exposed pups show impaired hypothalamic response to isolation, which is required to produce animals' USVs following isolation from the nest. Therefore, these results suggest that VPA-induced ASD pathology can be mediated by the loss of δ-catenin functions. Highlights: Prenatal exposure of valproic acid (VPA) in mice significantly reduces synaptic δ-catenin protein and AMPA receptor levels in the pups' brains.VPA treatment significantly impairs dendritic branching in cultured cortical neurons, which is reversed by increased δ-catenin expression.VPA exposed pups exhibit impaired communication such as ultrasonic vocalization.Neuronal activation linked to ultrasonic vocalization is absent in VPA-exposed pups.The loss of δ-catenin functions underlies VPA-induced autism spectrum disorder (ASD) in early childhood.

EMG Activity With Use of a Hands-Free Single Crutch vs a Knee Scooter.

BACKGROUND: Foot and ankle injuries frequently require a period of nonweightbearing, resulting in muscle atrophy. Our previous study compared a hands-free single crutch (HFSC) to standard axillary crutches and found increased muscle recruitment and intensity while using the HFSC. Knee scooters are another commonly prescribed nonweightbearing device. The purpose of this study is to examine the electromyographic (EMG) differences between an HFSC and knee scooter, in conjunction with device preference and perceived exertion. METHODS: A randomized crossover study was performed using 30 noninjured young adults. Wireless surface EMG electrodes were placed on the belly of the rectus femoris (RF), vastus lateralis (VL), lateral gastrocnemius (LG), and gluteus maximus (GM). Participants then ambulated along a 20-m walking area while 15 seconds of the gait cycle was recorded across 3 conditions: walking with a knee scooter, an HFSC, and with no assistive device. Mean muscle activity and peak EMG activity were recorded for each ambulatory modality. Immediately following testing, patient exertion and device preference was recorded. RESULTS: The RF, LG, and GM showed increased peak EMG activity percentage, and the LG showed increased mean muscle activity while using the HFSC compared with the knee scooter. When comparing the knee scooter and HFSC to walking, both showed increased muscle activity in the RF, VL, and LG but no difference in the GM. There was no statistical difference in participant preference, whereas the HFSC had a statistically significant higher perceived exertion than the knee scooter (P < .001). CONCLUSION: In this group of young, healthy noninjured volunteers, the HFSC demonstrated increased peak EMG activity in most muscle groups tested compared with the knee scooter. LEVEL OF EVIDENCE: Level II, prospective comparative study.