Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
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Universidade Federal de Goiás
Stroke is characterized by a disruption in the cerebral blood supply, leading to oxygen and glucose deprivation to the tissue. Cerebral ischemia involves enhanced glutamate release, abnormal NMDAR activation, and excitotoxicity. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission through NMDA receptors, suggesting an alternative stroke therapeutic strategy. This work investigated the neuroprotective and neurorestorative potential of GlyT1 inhibition in a mouse model of focal ischemia. Swiss mice subjected to permanent middle cerebral artery occlusion (MCAO) were randomized to receive three different doses of Sarcosine (125, 250, and 500 mg/kg) or vehicle before or after ischemia. Pretreatment with 250 and 500 mg/kg of Sarcosine led to neuroprotection against stroke, as demonstrated by reduction of infarct area and neurological deficits. Moreover, GluN2A/CaMKIV/CREB and BDNF/TrKB/Akt/mTOR pathways were enhanced by sarcosine. The sarcosine neuroprotection is also related to GluN2B subunit downregulation and a decrease in CaMKIIα phosphorylation. Additionally, we observed that post-stroke treatment with higher doses of Sarcosine improves the neurorepair process, which is evidenced by the marked reduction of the infarct area and motor deficits. Therefore, sarcosine pretreatment induced neuroprotection through the BDNF/TRKB and CaMKIV/CREB pathways, both processes trigged by NMDAR activity.
MARQUES, B. L. Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal. 2022. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022.