🧬 BDNF Extraction Viewer

Извлечено: 997 / 997 (100.0%) Средняя confidence: 0.13
← Назад к списку

Chrysin Ameliorates Valproic Acid Induced Autism Spectrum Behavioral Phenotypes Through Corticohippocampal Histone Deacetylase and Translational Modulation of SHANK3 Expression in Juvenile Rats.

PMID: 41699184 · DOI: 10.1007/s12031-026-02475-3 · Journal of molecular neuroscience : MN, 2026 · Ismaheel Akinwale Adeniyi, Samuel Adetunji Onasanwo
📄 Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by repetitive behaviors, social deficits, and comorbid phenotypes, with rising prevalence. Its unclear pathogenesis and symptom heterogeneity hinder therapy development. Chrysin, a flavone from bee products and plants, shows diverse biological effects but limited ASD studies. Therefore, this study examines chrysin's impact on ASD behaviors and comorbidities. Pregnant Wistar rats received 600 mg/kg valproic acid (VPA) on Embryonic day (ED) 12.5 intraperitoneally to induce ASD phenotypes. Neurodevelopmental milestones were evaluated on postnatal day (PND) 3-20. Twenty-seven male offspring were used for the study. The control (n = 9 ), the VPA-exposed offspring were randomly divided into two groups: a VPA + vehicle group (n = 9) and a VPA + chrysin treatment group (n = 9). The animals received distilled water or chrysin (100 mg/kg p.o) from PND21-42. Typical and atypical baseline behaviours were done on PND21 and repeated on PND42. Serum corticosterone, prefrontal cortex (pFC), and hippocampal (HPC) neurotransmitters, Histone deacetylase (HDAC), BDNF, and caspase-3 were evaluated with ELISA, while Shank3, p-AKT, and pS6 were evaluated with immunohistochemistry and Western blot. Data were analysed using One-way or Two-way ANOVA at α < 0.05. The VPA-exposed pups exhibit signs of developmental delay compared to the controls. Chrysin also ameliorated hyperalgesia (2.659 ± 0.2628vs4.257 ± 0.3272), depressive-like behaviour (68.86 ± 3.912vs138.5 ± 9.526), and anxiety (189.6 ± 20.58vs95.10 ± 7.716). Autistic-like, sociability (0.46 ± 0.039vs0.28 ± 0.06), and social novelty (0.77 ± 0.08vs-0.28 ± 0.19) were improved by Chrysin. Chrysin increased the level of serum corticosterone (22.45 ± 1.77vs13.90 ± 0.49) when compared to VPA-only. In the prefrontal cortex and hippocampus, the levels of serotonin, GABA, and dopamine increased, while glutamate levels decreased. The levels of HDAC (1.28 ± 0.12vs2.56 ± 0.10; 1.22 ± 0.11vs1.35 ± 0.18), and Caspase3 (10.33 ± 0.72vs16.79 ± 0.85; 4.50 ± 0.53vs6.45 ± 0.78) were reduced compared to VPA-only, while increasing the levels of BDNF (21.25 ± 0.63vs14.73 ± 0.57; 17.86 ± 1.23vs7.39 ± 0.56). Chrysin increased the expression of SHANK3(1.43 ± 0.1311vs0.6588 ± 0.02533; 0.8895 ± 0.1092 vs. 0.1961 ± 0.1401), p-AKT (0.8923 ± 0.04518vs0.2493 ± 0.03399; 1.011 ± 0.09692vs0.4969 ± 0.08145), and pS6 in the pFC and HPC. Chrysin may have ameliorated valproic acid-induced Autistic-like behaviours by upregulating epigenetic and translational control of scaffolding protein synthesis, and preserving neurotrophic signalling, in male Wistar rats exposed to VPA in utero.

Confidence: 0.36 · 19 полей извлечено
Идентификация (6 полей)
Target
SHANK3
0.95
Alt. target
SH3 and multiple ankyrin repeat domains 3
0.90
Protein family
SHANK family
0.90
Functional class
scaffolding protein
0.90
Subcellular loc.
0.00
Isoforms (metab/obesity)
0.00
Механизм действия (21 полей)
Mechanism
Chrysin ameliorates ASD phenotypes by upregulating epigenetic and translational control of scaffolding protein synthesis, preserving neurotrophic signaling, and modulating neurotransmitter levels.
0.90
Mutations (obesity/lean)
0.00
Activity (obesity)
0.00
Activity temporal
0.00
Energy balance
0.00
Appetite
0.00
Fat metabolism
0.00
Lipolysis
0.00
Thermogenesis
0.00
Muscle metabolism
0.00
Inflammation
0.00
Glucose metabolism
0.00
AA metabolism
0.00
Hormonal pathways
Chrysin increased serum corticosterone levels.
0.80
Cell death
Chrysin reduced caspase-3 levels, indicating decreased apoptosis.
0.80
Adipocyte fibrosis
0.00
Upstream (biochem)
Valproic acid (VPA) exposure in utero.
0.70
Upstream (physiol)
0.00
Downstream (biochem)
SHANK3, p-AKT, pS6, BDNF, HDAC, caspase-3, serotonin, GABA, dopamine, glutamate.
0.90
Downstream (physiol)
Improved sociability, social novelty, reduced hyperalgesia, depressive-like behavior, and anxiety.
0.90
PTMs
Phosphorylation of AKT and S6 (p-AKT, pS6).
0.80
Экспрессия (8 полей)
Tissue expression
SHANK3, p-AKT, pS6, BDNF, HDAC, caspase-3, serotonin, GABA, dopamine, glutamate in prefrontal cortex and hippocampus; serum corticosterone
0.90
In vitro
0.00
In vivo
Pregnant Wistar rats received 600 mg/kg VPA on ED 12.5; male offspring treated with chrysin 100 mg/kg p.o. from PND21-42; behavioral tests and biochemical assays
0.95
In silico
0.00
Genetic association
0.00
Ex vivo
0.00
Animal model
Wistar rats, VPA-induced autism model
0.95
Diet/model
VPA (valproic acid) prenatal exposure to induce ASD; chrysin treatment
0.90
Клиника (11 полей)
Drug
Chrysin
1.00
Indication
Autism spectrum disorder
0.90
Patient subgroups
Male Wistar rats exposed to valproic acid in utero
0.80
Safety concerns
0.00
Off-target
0.00
Trial stage
0.00
Pharma competitors
0.00
AE severity
0.00
MOA weight loss
0.00
Endpoints
0.00
Approved
False
0.90