Early environmental enrichment for autism spectrum disorder Fmr1 mice models has positive behavioral and molecular effects

Chen, Yu‐Shan; Zhang, Si-Ming; Yue, Chao-xiong; Xiang, Peng; Li, Jinquan; Wei, Zhen; Xu, Li‐Yan; Zeng, Yan

doi:10.1016/j.expneurol.2022.114033

Cited by 12 publications

(20 citation statements)

References 54 publications

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“…Several studies indicate that BDNF protein production is altered in the brain of Fmr1 KO mice and several FMRP functions are modulated by BDNF signaling [16][17][18]. The recent study has also shown that the expression pro le of BDNF during early phases of neuronal development and we found the correlation between BDNF-TrkB signaling and mature spines in young FXS mice [19]. In this sense, BDNF-TrkB pathway impairments during development maybe the key mechanisms underlying abnormal dendritic spine morphogenesis and cognitive dysfunction in FXS.…”

Section: Introductionsupporting

confidence: 67%

“…TrkB and PLCγ agonists improve neuronal morphology in primary neurons obtained from Fmr1 KO mice Since TrkB and PLCγ activation is down regulated and may cause the aberrant dendritic spines in Fmr1 KO mice [19], we asked if TrkB and PLCγ agonists could improve hippocampal neuronal morphology in vitro. Then we examined the dendritic length and branches in neurons treated with or without 7,8-DHF (TrkB agonist), m-3M3FBS (PLCγ agonist) or K252a (TrkB inhibitor).…”

Section: Resultsmentioning

confidence: 99%

“…3D, 3E, and 3F). Two-way ANOVA of branches and dendritic length showed a main effect of genotype [F (1,196) Our previous study has suggested that BDNF/TrkB-PLCγ1-CaMKII signaling is downregulated at the early stages of postnatal development in Fmr1 KO mice [19]. To investigate whether aberrant TrkB and the downstream signaling pathways would be rescued by TrkB agonist 7,8-DHF, we rst studied the activation status of p-TrkB, p-PLCγ, and p-CaMKII after treating P14 mice with 5 mg/kg 7,8-DHF daily for continuous 16 days (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…TEM experiments were conducted as the previous studies [19,34]. Samples were immersed in 1% osmium tetraoxide in PBS for 2h and then dehydrated in graded ethanol, and embedded in epoxy resin.…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

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Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway

et al. 2023

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Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and the most common known cause of autism spectrum disorders. FXS patients exhibit severe syndromic features and behavioral alterations, including anxiety, hyperactivity, impulsivity, and aggression, in addition to cognitive impairment and seizures. At present, there are no effective treatments or cures for FXS. Previously, we have found the divergence of BDNF-TrkB signaling trajectories is associated with spine defects in early postnatal developmental stages of Fmr1 KO mice. Here, young fragile X mice were intraperitoneal injection of 7,8-Dihydroxy avone (7,8-DHF), which is a high a nity tropomyosin receptor kinase B (TrkB) agonist. 7,8-DHF ameliorated morphological abnormities in dendritic spine and synaptic structure, and rescued synaptic and hippocampus-dependent cognitive dysfunction in young FXS mice. These observed improvement of 7,8-DHF involved decreased protein levels of BDNF, p-TrkB Y816 , p-PLCγ, and p-CaMKII in the hippocampus. In addition, 7,8-DHF intervention in primary hippocampal neurons increased p-TrkB Y816 through activating the PLCγ1-CaMKII signaling pathway leading to improvement of neuronal morphology.This study is the rst to account for early life synaptic impairments, neuronal morphological and cognitive delays in FXS in response to the abnormal BDNF-TrkB pathway. Present studies provide novel evidences about the effective early intervention in FXS mice at developmental stages as a strategy to produce powerful impacts on neural development, synaptic plasticity and behaviors.

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Section: Introductionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

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Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway

et al. 2023

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“…More recently, this line of research is expanding in order to understand if this type of early approach can have effects on social abilities and also, in this case, results appear very promising. In animal models, profound and long-term beneficial effects of early social environmental stimulation were found, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases [23][24][25].…”

Section: Neurobiology Of Early Intervention In Asdmentioning

confidence: 92%

What Therapy for My Child? Features, Strengths, and Gaps to Fill for the Implementation of Early Autism Interventions

Purpura¹,

Contaldo²

2023

Autism Spectrum Disorders - Recent Advances and New Perspectives

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Scientific literature suggests the neurobiological value of early intervention for children at risk of ASD and of other neurodevelopmental disorders, because it is based on the promotion of brain plasticity mechanisms in an ecological, noninvasive, and evidence-based way. Moreover, several authors suggest the greatest efficacy of early rehabilitation programs, involving both the parents and the children, is to improve not only sensory-motor and cognitive outcomes but also child-parent interactions and the wellness of the familiar system. In this chapter, the neurobiological fundaments and features for the early intervention and the most recent early approaches for children at risk of ASD (behavioral, developmental, naturalistic developmental behavioral, and parent-mediated interventions) will be explained.

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Beneficial effects and neurobiological aspects of environmental enrichment associated to major depressive disorder and autism spectrum disorder

Manosso¹,

Broseghini²,

Campos³

et al. 2022

Brain Research Bulletin

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Early environmental enrichment for autism spectrum disorder Fmr1 mice models has positive behavioral and molecular effects

Cited by 12 publications

References 54 publications

Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway

Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway

What Therapy for My Child? Features, Strengths, and Gaps to Fill for the Implementation of Early Autism Interventions

Beneficial effects and neurobiological aspects of environmental enrichment associated to major depressive disorder and autism spectrum disorder

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