RESUMO
Introduction: A neurodevelopmental disorder, autism is typically identified with three primary behavioral consequences, such as social impairment, communication problems, and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid is formed biologically by the gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms. Methods: To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg/po on the 21st, 22nd, and 23rd postnatal days). Rats also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood-brain barrier permeability. Results: Ruthenium red was found to counter the propionic acid-induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage, and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. Conclusion: Ryanodine receptor antagonists presented a neuroprotective effect in propionic acid-induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition. Highlights: Ruthenium red can reduce the propionic acid-induced anxiety of rats with autism.Ruthenium red can improve the propionic acid-induced changes in repetitive behavior of rats with autism.Ruthenium red can reduce the propionic acid-induced social behavior dysfunction in rats with autism. Plain Language Summary: Autism is a complex heterogeneous neurodevelopmental disorder mainly diagnosed with social behavior dysfunction, communication problems, and repetitive behavior. Due to high comorbidity and multiple unknown factors involvement, its exact etiology remains unclear, and so no successful treatment is available. Among the environmentally produced models of autism in rats, the most common is created by propionic acid (PPA). With short-chain type fatty acid, PPA is one of the mediators for the cycle of cell metabolism. This study attempted to study the effect of a ryano-dine receptor antagonist (Ruthenium red) on PPA-induced Anxiety, social behavior dysfunction, and repeated behaviors in rats with autism. The results showed the modulatory effects of Ruthenium red PPA-induced conditions including social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes in rats with autism.
RESUMO
Ischemic stroke is a medical condition that arises because of poor blood supply to the brain. Reperfusion being salvage to the brain further causes, exacerbation of tissue injury, known as reperfusion injury. Ischemic preconditioning (IPC) has been known to provide benefits against ischemia reperfusion (I/R) injury. Dopamine D2/D3 receptor mediated several pathways are also reported as mediators in the IPC mediated neuroprotection. This study investigates the possible involvement of D2/D3 receptor activation in IPC mediated neuroprotection in the I/R brain. Global cerebral ischemia/reperfusion (GCI/R) injury in swiss albino mice was induced by occluding the common carotid arteries for 17 min, followed by 24 h reperfusion. IPC was provided by giving 3 episodes of I/R prior to Ischemia (17 min). Morris water maze (MWM) was used to assess the spatial learning, memory and Rota rod, lateral push test as well as inclined beam test were conducted to assess the motor functions in animals. Cerebral oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE, infarct size (% weight and % volume), and histopathological changes were also assessed. Haloperidol (0.05 mg/kg, i.p) was used to antagonize the effects of D2/D3 receptor activation. I/R animals showed reduction in memory, motor function, increase in cerebral oxidative stress, inflammation, AChE activity, infarct size and histopathological changes. Episodes of IPC prior to ischemia, attenuated the deleterious effects of I/R injury. Administration of haloperidol abolished the protective effects of IPC. Hence, it may be concluded that IPC mediated neuroprotection may involves dopamine D2/D3 receptor activation in mice.
