Targeting Brain Plasticity: Vagal Nerve Stimulation as a Therapy for Autism-Like Symptoms in a Valproic Acid Mouse Model

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Çalıkuşu A., İnce M. S., Belen H. B., Atalar K., Yığman Z., Abbasoğlu Topa E. G., ...Daha Fazla

DEVELOPMENTAL NEUROBIOLOGY, cilt.1, sa.1, ss.1-22, 2025 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/dneu.23019
  • Dergi Adı: DEVELOPMENTAL NEUROBIOLOGY
  • Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, EMBASE, MEDLINE, Psycinfo
  • Sayfa Sayıları: ss.1-22
  • Gazi Üniversitesi Adresli: Evet

Özet

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition defined by social deficits, stereotypical

or repetitive behaviors, and anxiety. This study evaluates the therapeutic potential of transauricular vagal nerve stimulation

(tVNS) ina valproic acid (VPA)-induced mousemodelof ASD. The studycomprisedthree groups:thecontrol+ sham(saline-

treated offsprings receiving sham stimulation), the autistic + sham (VPA-treated offspring receiving sham stimulation), and

the autistic + tVNS (VPA-treated offsprings receiving tVNS). Male C57BL/6 mice exposed to VPA on embryonic day 12.5 were

evaluatedforbehavioralandneurobiologicalalterations.tVNSwasappliedtwiceweeklyfor3weekstoinvestigateitseffectson

sociability,anxiety-likebehaviors,neurogenesismarkers,andapoptosispathways.Behavioraltesting,includingthethree-chamber

test, mirrored chamber test, open field test, and elevated plus maze, revealed that tVNS significantly improved sociability and

socialpreferenceindices,reducedsocialanxiety,anddecreasedgeneralanxiety-likebehaviorsinVPA-inducedmice.Histological

and immunohistochemical analyses have shown a decrease in neuron density, brain-derived neurotrophic factor (BDNF), and

doublecortin (DCX) expression in the hippocampus, amygdala, and prefrontal cortex of VPA-induced mice. Additionally, the

increaseincaspase-3immunoreactivityindicatesincreasedapoptosis.tVNStreatmentrestoredBDNFandDCXlevels,promoting

neurogenesisandsynapticplasticitywhilesignificantlyreducingcaspase-3-mediatedapoptosisinaffectedbrainregions.These

findingssuggestthattVNSmaycounteracttheneuralandbehavioraldeficitsassociatedwithASDbymodulatingneurogenesis,

neuronalplasticity,andapoptosis.ThestudyhighlightstVNSasapotentialtherapeuticinterventionforASD,emphasizingitsrole

intargetingbothbehavioralalterationsandunderlyingneurobiologicalmechanisms.