Author:
Luhach Kanishk,Kulkarni Giriraj T.,Singh Vijay P.,Sharma Bhupesh
Abstract
Hyperserotonemia, during the early developmental phase, generates behavioral and biochemical phenotypes associated with autism
spectrum disorder (ASD) in rats. Phosphodiesterase‑1 (PDE1) inhibitors are known to provide benefits in various brain conditions. We
investigated the role of a selective PDE1 inhibitor, vinpocetine on ASD‑related behavioral phenotypes (social behavioral deficits, repetitive
behavior, anxiety, and hyperlocomotion) in a developmental hyperserotonemia (DHS) rat model. Also, effects on biochemical markers
related with neuronal function brain derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein
(pCREB), inflammation interleukins (IL‑6 and IL‑10) and tumor necrosis factor–alpha (TNF‑α), and oxidative stress (TBARS and GSH) were
studied in important brain areas (frontal cortex, cerebellum, hippocampus, and striatum). Administration of 5‑methoxytryptamine
(5‑MT) to rats prenatally (gestational day 12) and in early developmental stages postnatal day (PND 0 – PND 20), resulted in impaired
behavior and brain biochemistry. Administration of vinpocetine daily (10 and 20 mg/kg) to 5‑MT rats from PND 21 to PND 48 resulted
in an improvement of behavioral deficits. Also, vinpocetine administration significantly increased the levels of BDNF, ratio of pCREB/
CREB, IL‑10, and GSH, and significantly decreased TNF‑α, IL‑6, and TBARS levels in different brain areas. Finally, our correlation analysis
indicated that behavioral outcomes were significantly associated with the biochemical outcome. Vinpocetine, a selective PDE1 inhibitor,
rectified important behavioral phenotypes related with ASD, possibly by improving markers of neuronal function, brain inflammation,
and brain oxidative stress. Thus, PDE1 could be a potential target for pharmacological interventions and furthering our understanding
of ASD pathogenesis.
Publisher
The Nencki Institute of Experimental Biology, Polish Academy of Sciences
Subject
General Medicine,General Neuroscience
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献