Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
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2022-11-04
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Universidade Federal de Goiás
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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.
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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.