A single administration of ascorbic acid rapidly reverses depressive-like behavior and hippocampal synaptic dysfunction induced by corticosterone in mice
A single administration of ascorbic acid rapidly reverses depressive-like behavior and hippocampal synaptic dysfunction induced by corticosterone in mice
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DOI：
10.1016/j.cbi.2021.109476
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发表时间：
2021-04-27
影响因子：
5.1
通讯作者：
Rodrigues, Ana Lucia S.
中科院分区：
文献类型：
--
作者：
Fraga, Daiane B.;Camargo, Anderson;Rodrigues, Ana Lucia S.
Ketamine is the prototype for glutamate-based fast-acting antidepressants. The establishment of ketamine-like drugs is still a challenge and ascorbic acid has emerged as a candidate. This study investigated the ascorbic acid's ability to induce a fast antidepressant-like response and to improve hippocampal synaptic markers in mice subjected to chronic corticosterone (CORT) administration. CORT was administered for 21 days, followed by a single administration of ascorbic acid (1 mg /Kg, p.o.), ketamine (1 mg /Kg, i.p.) or fluoxetine (10 mg /Kg, p.o.) in mice. Depressive-like behavior, hippocampal synaptic proteins immunocontent, dendrite spines density in the dentate gyrus (DG) were analyzed 24 h following treatments. The administration of ascorbic acid or ketamine, but not fluoxetine, counteracted CORT-induced depressive-like behavior in the tail suspension test (TST). CORT administration reduced PSD-95, GluA1, and synapsin (synaptic markers) immunocontent, and these alterations were reversed by ascorbic acid or ketamine, but only ketamine reversed the CORT-induced reduction on GluA1 immunocontent. In the ventral and dorsal DG, CORT decreased filopodia-, thin- and stubby-shaped spines, while ascorbic acid and ketamine abolished this alteration only in filopodia spines. Ascorbic acid and ketamine increased mushroom-shaped spines density in ventral and dorsal DG. Therefore, the results show that a single administration of ascorbic acid, in a way similar to ketamine, rapidly elicits an antidepressant-like response and reverses hippocampal synaptic deficits caused by CORT, an effect associated with increased levels of synaptic proteins and dendritic remodeling.
