Transcutaneous Electrical Acupoint Stimulation in Early Life Changes Synaptic Plasticity and Improves Symptoms in a Valproic Acid-Induced Rat Model of Autism

Autism spectrum disorder (ASD) is a developmental disorder characterized by social behavior deficit in childhood without satisfactory medical intervention. Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive technique derived from acupuncture and has been shown to have similar therapeutic effects in many diseases. Valproic acid- (VPA-) induced ASD is a known model of ASD in rats. The therapeutic efficacy of TEAS was evaluated in the VPA model of ASD in the present study. The offspring of a VPA-treated rat received TEAS in the early life stage followed by a series of examinations conducted in their adolescence. The results show that following TEAS treatment in early life, the social and cognitive ability in adolescence of the offspring of a VPA rat were significantly improved. In addition, the abnormal pain threshold was significantly corrected. Additional studies demonstrated that the dendritic spine density of the primary sensory cortex was decreased with Golgi staining. Results of the transcriptomic study showed that expression of some transcription factors such as the neurotrophic factor were downregulated in the hypothalamus of the VPA model of ASD. The reduced gene expression was reversed following TEAS. These results suggest that TEAS in the early life stage may mitigate disorders of social and recognition ability and normalize the pain threshold of the ASD rat model. The mechanism involved may be related to improvement of synaptic plasticity.

Download Full-text

Characterization and rescue by oxytocin of an atypical thermo-sensory reactivity in neonatal mice lacking the autism-associated gene Magel2

10.1101/869487 ◽

2019 ◽

Author(s):

Laura Caccialupi Da Prato ◽

Dina Abdallah ◽

Vanessa Point ◽

Fabienne Schaller ◽

Emilie Pallesi-Pocachard ◽

...

Keyword(s):

Early Life ◽

Life Stage ◽

Early Life Stage ◽

Autism Spectrum ◽

Induced Response ◽

Cool Temperature ◽

Sensory Stimuli ◽

Sensory Reactivity ◽

Neonatal Mice ◽

Thermoregulatory Function

ABSTRACTAtypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage is unknown. Here we investigated cool thermosensibility during the first week of mouse life. In response to cool temperature exposure control neonates undertake innate behaviors by eliciting low-latency ultrasonic vocalization. However, we found that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool stimuli while long-term thermoregulatory function, namely nonshivering thermogenesis, is active. Investigation of the sensory pathway revealed abnormal cool-induced response in the medial preoptic area. Importantly, intranasal administration of oxytocin can rescue this thermosensory reactivity. In addition, chemogenetic inactivation in control neonates of hypothalamic oxytocin neurons reproduces the coolness response failure observed in Magel2 mutants. Collectively, these findings establish for the first-time impairments of thermal lower-reactivity in a mouse model of ASD with deletion of Magel2 gene during early life period and reveal that the oxytocinergic system regulates this neonatal cool thermosensibility.

Download Full-text