School of Psychology, Behavioural Neurogenetics Group, Victoria University of Wellington, Kelburn, Wellington, New Zealand.
School of Biological Sciences, Victoria University of Wellington, Kelburn, Wellington, New Zealand.
J Mol Neurosci. 2021 Nov;71(11):2210-2218. doi: 10.1007/s12031-020-01764-9. Epub 2021 Jan 5.
Dysregulation of the serotonergic system has been reported to have a significant role in several neurological disorders including depression, autism and substance abuse disorders. Changes in the expression of the serotonin transporter (SERT) through polymorphisms in the regulatory regions of the SERT gene have been associated, but not yet been conclusively linked to, neuropsychiatric disorders. In turn, dendritic spine structure and function are critical for neuronal function and the disruption of dendritic spine formation at glutamatergic synapses is a hallmark of several neuropsychiatric disorders. To understand the effect of SERT depletion on dendritic spine formation, neuronal cultures were established from the cortex of postnatal day 0-1 SERT knockout (KO) rats. Cortical neurons were subsequently allowed to mature to 21 days in vitro, and dendritic spine density was assessed using immunocytochemical co-labelling of drebrin and microtubule associated protein 2. Genetic knockout of the SERT had a gene-dose effect on dendritic spine densities of cortical neurons. The results of this paper implicate SERT function with the formation of dendritic spines at glutamatergic synapses, thereby offering insight into the aetiology of several neuropathologies.
血清素能系统的失调已被报道在包括抑郁症、自闭症和物质滥用障碍在内的几种神经紊乱中起重要作用。通过 SERT 基因调节区域的多态性，发现 5-羟色胺转运体（SERT）的表达变化与神经精神障碍有关，但尚未有明确的关联。反过来，树突棘的结构和功能对神经元功能至关重要，谷氨酸能突触形成的树突棘形成中断是几种神经精神疾病的标志。为了了解 SERT 耗竭对树突棘形成的影响，我们从出生后 0-1 天的 SERT 敲除（KO）大鼠的皮层中建立了神经元培养物。随后，将皮层神经元在体外培养 21 天，并使用 drebrin 和微管相关蛋白 2 的免疫细胞化学共标记来评估树突棘密度。SERT 的基因敲除对皮质神经元树突棘密度有基因剂量效应。本文的结果表明 SERT 功能与谷氨酸能突触处的树突棘形成有关，从而为几种神经病理学的发病机制提供了新的见解。
