Reduced risk aversion and impaired short-term memory in juvenile rats with malformation of cortical development

Kim, Eun Jin; Lee, Minyoung; Kim, Min-Jee; Yum, Mi‐Sun

doi:10.1016/j.bbr.2021.113442

Cited by 4 publications

(1 citation statement)

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“…On P40, the Y-maze test was performed as previously described [23] with a computerized motion-tracking software (SMART 3.0; Panlab S.L.U., Barcelona, Spain). An arm entry was counted when all four limbs were inside the arm, and the number of novel arm entries divided by the total number of entries (i.e., the number of novel and familiar arm entries) was multiplied by 100 to calculate the novelty preference (NP) index.…”

Section: Y-maze Test At P40mentioning

confidence: 99%

Insulin-Like Growth Factor-1 Promotes Synaptogenesis Signaling, a Major Dysregulated Pathway in Malformation of Cortical Development, in a Rat Model

Lee

Kim

et al. 2023

Mol Neurobiol

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Malformation of cortical development (MCD) is one of the main causes of intractable epilepsy in childhood. We explored a treatment based on molecular changes using an infant rat model of methylazoxymethanol (MAM)-induced MCD established by injecting MAM at gestational day 15. The offspring were sacri ced on postnatal day (P) 15 for proteomic analysis, which revealed signi cant downregulation in the synaptogenesis signaling pathway in the cortex of MCD rats. Recombinant human insulin-growth factor-1 (rhIGF-1) was injected from P12 to P14 twice daily and the effect of IGF1 on Nmethyl-D-aspartate (NMDA)-induced spasms (15 mg/kg of NMDA, i.p.) was tested; the onset of P15 single spasm was signi cantly delayed (p = 0.002) and the number of spasms decreased (p < 0.001) in rhIGF1-pretreated rats (n = 17) as compared to those in VEH-treated rats (n = 18). Electroencephalographic monitoring during spasms showed signi cantly reduced spectral entropy and event-related spectral dynamics of fast oscillation in rhIGF-1 treated rats. Magnetic resonance spectroscopy of the retrosplenial cortex showed decreased glutathione (GSH) (p = 0.039) and signi cant developmental changes in GSH, phosphocreatine (PCr), and total creatine (tCr) (p = 0.023, 0.042, 0.015, respectively) after rhIGF1 pretreatment. rhIGF1 pretreatment signi cantly upregulated expression of cortical synaptic proteins such as PSD95, AMPAR1, AMPAR4, NMDAR1, and NMDAR2A (p < 0.05). Thus, early rhIGF-1 treatment could promote synaptic protein expression, which was signi cantly downregulated by prenatal MAM exposure, and effectively suppress NMDA-induced spasms. Early IGF1 treatment should be further investigated as a therapeutic strategy in infants with MCD-related epilepsy.

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Section: Y-maze Test At P40mentioning

confidence: 99%