Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS 90035 003, Brazil.
Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS 90035 003, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 2;98:109776. doi: 10.1016/j.pnpbp.2019.109776. Epub 2019 Nov 9.
Longitudinal and some experimental studies have showed the potential of caffeine to counteract some depressive behaviors and synaptic dysfunctions. In this study, we investigated the potential of caffeine in preventing behavioral outcomes, neurodegeneration and synaptic proteins alterations in a mice model of agitated depression by bilateral olfactory bulbectomy (OB). For this purpose, bulbectomized mice received caffeine (0.3 g/L and 1.0 g/L, drinking water), during the active cycle, for seven weeks (two before the surgery and throughout five weeks after OB). Caffeine prevented OB-induced hyperactivity and recognition memory impairment and rescue self care and motivational behavior. In the frontal cortex, bulbectomized mice presented increase in the adenosine A receptors (AR) and GFAP, while adenosine A receptors (AR) increased in the hippocampus and striatum and SNAP-25 was decreased in frontal cortex and striatum. Caffeine increased AR in the striatum of bulbectomized mice and in SHAM-water group caffeine increased AR in the striatum and decreased SNAP-25 in the frontal cortex. Astrogliosis observed in the polymorphic layer of the dentate gyrus of OB mice was prevented by caffeine as well as the neurodegeneration in the striatum and piriform cortex. Based on these behavioral and neurochemical evidences, caffeine confirms its efficacy in preventing neurodegeneration associated with memory impairment and may be considered as a promising therapeutic tool in the prophylaxis and/or treatment of depression.
纵向和一些实验研究表明，咖啡因具有对抗一些抑郁行为和突触功能障碍的潜力。在这项研究中，我们通过双侧嗅球切除术（OB）研究了咖啡因在预防激动性抑郁小鼠模型中的行为结果、神经退行性变和突触蛋白改变的潜力。为此，在手术前两周和 OB 后五周期间，嗅球切除术小鼠接受了咖啡因（0.3 g/L 和 1.0 g/L，饮用水）。咖啡因可预防 OB 引起的过度活跃和识别记忆障碍，并挽救自我护理和动机行为。在前额叶皮层中，OB 小鼠的腺苷 A 受体（AR）和 GFAP 增加，而海马体和纹状体中的 AR 增加，前额叶皮层和纹状体中的 SNAP-25 减少。咖啡因增加了 OB 小鼠纹状体中的 AR，而在 SHAM-水组中，咖啡因增加了纹状体中的 AR，并减少了前额叶皮层中的 SNAP-25。咖啡因还可以预防 OB 小鼠齿状回多形层中的神经胶质增生以及纹状体和梨状皮层中的神经退行性变。基于这些行为和神经化学证据，咖啡因证实了其在预防与记忆障碍相关的神经退行性变方面的疗效，并且可能被认为是预防和/或治疗抑郁症的有前途的治疗工具。
