Roversi Karine, Buizza Carolina, Brivio Paola, Calabrese Francesca, Verheij Michel M M, Antoniazzi Caren T D, Burger Marilise E, Riva Marco A, Homberg Judith R
Department of Physiology and Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, Brazil.
Department of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano, Milan, Italy.
Front Behav Neurosci. 2020 Aug 12;14:142. doi: 10.3389/fnbeh.2020.00142. eCollection 2020.
The serotonin transporter (SERT) gene, especially the short allele of the human serotonin transporter linked polymorphic region (5-HTTLPR), has been associated with the development of stress-related neuropsychiatric disorders. In line, exposure to early life stress in SERT knockout animals contributes to anxiety- and depression-like behavior. However, there is a lack of investigation of how early-life exposure to beneficial stimuli, such as tactile stimulation (TS), affects later life behavior in these animals. In this study, we investigated the effect of TS on social, anxiety, and anhedonic behavior in heterozygous SERT knockouts rats and wild-type controls and its impact on gene expression in the basolateral amygdala. Heterozygous SERT rats were submitted to TS during postnatal days 8-14, for 10 min per day. In adulthood, rats were assessed for social and affective behavior. Besides, brain-derived neurotrophic factor (Bdnf) gene expression and its isoforms, components of glutamatergic and GABAergic systems as well as glucocorticoid-responsive genes were measured in the basolateral amygdala. We found that exposure to neonatal TS improved social and affective behavior in SERT animals compared to naïve SERT animals and was normalized to the level of naïve SERT animals. At the molecular level, we observed that TS affected Bdnf, the glucocorticoid-responsive genes Nr4a1, Gadd45β, the co-chaperone Fkbp5 as well as glutamatergic and GABAergic gene expression markers including the enzyme Gad67, the vesicular GABA transporter, and the vesicular glutamate transporter genes. Our results suggest that exposure of SERT rats to neonatal TS can normalize their phenotype in adulthood and that TS alters the expression of plasticity and stress-related genes in the basolateral amygdala. These findings demonstrate the potential effect of a supportive stimulus in SERT rodents, which are more susceptible to develop psychiatric disorders.
血清素转运体(SERT)基因,尤其是人类血清素转运体相关多态性区域(5-HTTLPR)的短等位基因,与应激相关神经精神疾病的发生有关。同样,SERT基因敲除动物早年暴露于应激中会导致类似焦虑和抑郁的行为。然而,目前缺乏关于早年暴露于有益刺激(如触觉刺激,TS)如何影响这些动物后期行为的研究。在本研究中,我们调查了TS对杂合子SERT基因敲除大鼠和野生型对照大鼠的社交、焦虑和快感缺失行为的影响及其对基底外侧杏仁核基因表达的影响。在出生后第8 - 14天,每天对杂合子SERT大鼠进行10分钟的TS处理。成年后,对大鼠的社交和情感行为进行评估。此外,还测量了基底外侧杏仁核中脑源性神经营养因子(Bdnf)基因及其亚型的表达、谷氨酸能和γ-氨基丁酸能系统的成分以及糖皮质激素反应基因的表达。我们发现,与未经处理的SERT动物相比,新生儿期暴露于TS可改善SERT动物的社交和情感行为,且其水平恢复至未经处理的SERT动物水平。在分子水平上,我们观察到TS影响了Bdnf、糖皮质激素反应基因Nr4a1、Gadd45β、辅助伴侣蛋白Fkbp5以及谷氨酸能和γ-氨基丁酸能基因表达标志物,包括酶Gad67、囊泡γ-氨基丁酸转运体和囊泡谷氨酸转运体基因。我们的结果表明,SERT大鼠新生儿期暴露于TS可使其成年后的表型正常化,且TS改变了基底外侧杏仁核中可塑性和应激相关基因的表达。这些发现证明了支持性刺激对更易患精神疾病的SERT啮齿动物的潜在作用。