Postnatal Oxytocin Treatment and Cognitive Function in Fragile X
脆性 X 肌瘤的产后催产素治疗和认知功能
基本信息
- 批准号:10611408
- 负责人:
- 金额:$ 47.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-05 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:ASD patientAcuteAddressAdultAffectAgonistAnimal ModelBehaviorBehavioralBrainBrain regionBrain-Derived Neurotrophic FactorChildChildhoodCognitiveDTR geneDevelopmentDiseaseElectrophysiology (science)ElementsEpidermal Growth Factor ReceptorEpisodic memoryExcitatory SynapseExhibitsFMR1FemaleFragile X SyndromeFutureGenetic TechniquesGoalsHippocampusHypothalamic structureImpaired cognitionInheritedInhibitory SynapseIntellectual functioning disabilityKnockout MiceKnowledgeLearningLifeLocationLong-Term PotentiationMeasuresMediatingMemoryMemory impairmentModelingMorphologyNeurobiologyNeurodevelopmental DisorderNeuronsNeuropeptidesNeurotrophic Tyrosine Kinase Receptor Type 2OdorsOxytocinOxytocin ReceptorPeptidesPhenotypePhysiologicalProcessPropertyProteinsReceptor Protein-Tyrosine KinasesRegimenRegulationRodent ModelRoleRouteSignal TransductionSocial BehaviorSocial InteractionStereotyped BehaviorStructureSynapsesSynaptic ReceptorsSynaptic plasticitySystemTechniquesTestingTherapeuticThinkingTrophic Factor ReceptorVertebral columnWild Type MouseWorkautism spectrum disordercellular targetingcognitive functioncomorbiditycritical developmental periodcritical perioddesigndevelopmental diseaseearly phase clinical trialimprovedindividuals with autism spectrum disorderinterestmalememory encodingmouse modelmutantnovelpersonal narrativespostnatalpostnatal periodresponserestorationsexsocialsynaptic functiontherapeutic candidatetherapeutically effective
项目摘要
Autism Spectrum Disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder with high co-
morbidity for intellectual disability. This includes difficulties forming episodic, personal narrative, memories that
are critical for orderly thinking and organizing future behaviors. Episodic memory deficits are thus thought to be
major contributors to cognitive difficulties associated with autism. Many brain changes underlying abnormalities
in ASD appear in childhood suggesting the possibility for effective therapeutic strategies targeting brain
maturation. One candidate therapeutic is the hypothalamic peptide Oxytocin (OXT). Postnatal OXT treatment
improves social behavior in animal models of ASDs and recent work indicates that treatment in childhood
improves social interactions in autistic individuals. OXT acutely facilitates forms of synaptic plasticity, but there
has been little experimental consideration of possible enduring effects of postnatal OXT treatment on learning
and no analyses of effects on episodic memory. We examined this possibility using intranasal OXT (iOXT)
treatment in the Fmr1 KO mouse model of Fragile X Syndrome, and novel paradigms for analyses of `What,
When and Where' encoding. Our preliminary results show that in Fmr1 KOs iOXT treatments during the
second postnatal week (P7-13) fully rescue hippocampal field CA1 long-term potentiation, object location
memory, object identity (What) learning, and social recognition as assessed in adulthood (i.e., >40d after the
last treatment). These findings raise the exciting possibility that a limited period of early life OXT treatment can
effect a life-long rescue of a critical element of cognitive function in ASD. They also raise questions as to the
breadth of effects iOXT has on behavior and the mechanisms involved; these questions will be addressed in
the proposed studies. Aim 1 studies will test if postnatal iOXT treatment of male and female Fmr1 KO mice
rescues encoding for the three major components of episodic memory, social recognition and stereotypic
behavior as assessed in adulthood, and if effects depend on native OXT efflux. We will also determine if there
is a critical period for enduring iOXT effects on behavior. Aim 2 will use electrophysiological recordings of
evoked responses and network activity, analyses of synaptic proteins and signaling, and measures of neuronal
arbors to test if postnatal iOXT treatment normalizes neurobiological processes in the distinct hippocampal
subdivisions related to episodic memory encoding. Finally, Aim 3 will test the hypothesis that early life iOXT
leads to activation of synaptic trophic factor receptors (EGFR, TrkB) in hippocampus, thereby suggesting a
direct route for OXT effects on maturational changes in the structure. Overall, the proposed studies will greatly
expand our current knowledge of OXT actions in the young brain, including potentially critical roles in
regulating hippocampal development and synaptic function. Moreover, the results will lay the groundwork for
designing novel, early life regimens to optimize hippocampal maturation and function, and to rescue the
encoding of episodic memories in ASD and related developmental disorders.
自闭症谱系障碍(Autism Spectrum Disorder, ASD)是一种普遍存在的异质性神经发育障碍
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Christine M Gall其他文献
Christine M Gall的其他文献
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{{ truncateString('Christine M Gall', 18)}}的其他基金
Postnatal Oxytocin Treatment and Cognitive Function in Fragile X
脆性 X 肌瘤的产后催产素治疗和认知功能
- 批准号:
10383734 - 财政年份:2021
- 资助金额:
$ 47.6万 - 项目类别:
Postnatal Oxytocin Treatment and Cognitive Function in FragileX
FragileX 的产后催产素治疗和认知功能
- 批准号:
10842114 - 财政年份:2021
- 资助金额:
$ 47.6万 - 项目类别:
ICAL: Impact of Cannabinoids Across Lifespan: Pilot Project Core
ICAL:大麻素对整个生命周期的影响:试点项目核心
- 批准号:
10188477 - 财政年份:2018
- 资助金额:
$ 47.6万 - 项目类别:
ICAL: Impact of Cannabinoids Across Lifespan: Cellular Project
ICAL:大麻素对整个生命周期的影响:细胞项目
- 批准号:
10188479 - 财政年份:2018
- 资助金额:
$ 47.6万 - 项目类别:
Loss and rescue of endocannabinoid-dependent LTP and memory in Fragile-X model mice
Fragile-X 模型小鼠内源性大麻素依赖性 LTP 和记忆的丧失与挽救
- 批准号:
9332463 - 财政年份:2016
- 资助金额:
$ 47.6万 - 项目类别:
Loss and rescue of endocannabinoid-dependent LTP and memory in Fragile-X model mice
Fragile-X 模型小鼠内源性大麻素依赖性 LTP 和记忆的丧失与挽救
- 批准号:
9752269 - 财政年份:2016
- 资助金额:
$ 47.6万 - 项目类别:
Loss and rescue of endocannabinoid-dependent LTP and memory in Fragile-X model mice
Fragile-X 模型小鼠内源性大麻素依赖性 LTP 和记忆的丧失与挽救
- 批准号:
9502329 - 财政年份:2016
- 资助金额:
$ 47.6万 - 项目类别:
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