Diniz Danielle M, Calabrese Francesca, Brivio Paola, Riva Marco A, Grandjean Joanes, Homberg Judith R
Centre for Neuroscience, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The Netherlands.
Department of Pharmacological and Biomolecular Sciences, Universita' degli Studi di Milano, 20133 Milano, Italy.
Int J Mol Sci. 2021 May 10;22(9):5040. doi: 10.3390/ijms22095040.
BDNF plays a pivotal role in neuroplasticity events, vulnerability and resilience to stress-related disorders, being decreased in depressive patients and increased after antidepressant treatment. BDNF was found to be reduced in patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT) is one of the animal models used to investigate the underlying molecular mechanisms of depression in humans. They present decreased BDNF levels, and anxiety- and depression-like behavior. To investigate whether upregulating BDNF would ameliorate the phenotype of SERT rats, we overexpressed BDNF locally into the ventral hippocampus and submitted the animals to behavioral testing. The results showed that BDNF overexpression in the vHIP of SERT rats promoted higher sucrose preference and sucrose intake; on the first day of the sucrose consumption test it decreased immobility time in the forced swim test and increased the time spent in the center of a novel environment. Furthermore, BDNF overexpression altered social behavior in SERT rats, which presented increased passive contact with test partner and decreased solitary behavior. Finally, it promoted decrease in plasma corticosterone levels 60 min after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential target to new therapeutic approaches to improve depressive symptoms.
脑源性神经营养因子（BDNF）在神经可塑性事件、对与应激相关疾病的易感性和恢复力中起关键作用，在抑郁症患者中水平降低，而在抗抑郁治疗后升高。研究发现，携带血清素转运体启动子区域（5-HTTLPR）人类多态性的患者中BDNF水平降低。血清素基因敲除大鼠（SERT）是用于研究人类抑郁症潜在分子机制的动物模型之一。它们表现出BDNF水平降低以及焦虑样和抑郁样行为。为了研究上调BDNF是否会改善SERT大鼠的表型，我们在腹侧海马局部过表达BDNF，并对动物进行行为测试。结果表明，SERT大鼠腹侧海马中BDNF的过表达促进了更高的蔗糖偏好和蔗糖摄入量；在蔗糖消耗测试的第一天，它减少了强迫游泳测试中的不动时间，并增加了在新环境中心停留的时间。此外，BDNF过表达改变了SERT大鼠的社交行为，使其与测试伙伴的被动接触增加，孤独行为减少。最后，它促进了束缚应激60分钟后血浆皮质酮水平的降低。总之，调节SERT大鼠腹侧海马中BDNF IV的水平导致了积极的行为结果，将腹侧海马中BDNF的上调作为改善抑郁症状的新治疗方法的潜在靶点。
