Spanaki Cleanthe, Sidiropoulou Kyriaki, Petraki Zoe, Diskos Konstantinos, Konstantoudaki Xanthippi, Volitaki Emmanouela, Mylonaki Konstantina, Savvaki Maria, Plaitakis Andreas
Department of Neurology, School of Health Sciences, University of Crete, Voutes, Iraklion, Crete, Greece.
PaGNI University Hospital of Irakleio, Neurology Department, Iraklion, Crete, Greece.
iScience. 2024 Jan 19;27(2):108821. doi: 10.1016/j.isci.2024.108821. eCollection 2024 Feb 16.
The human brain is characterized by the upregulation of synaptic, mainly glutamatergic, transmission, but its evolutionary origin(s) remain elusive. Here we approached this fundamental question by studying mice transgenic (Tg) for , a human gene involved in glutamate metabolism that emerged in the hominoid and evolved concomitantly with brain expansion. We demonstrate that Tg mice express the human enzyme in hippocampal astrocytes and CA1-CA3 pyramidal neurons. LTP, evoked by theta-burst stimulation, is markedly enhanced in the CA3-CA1 synapses of Tg mice, with patch-clamp recordings from CA1 pyramidal neurons revealing increased sNMDA currents. LTP enhancement is blocked by D-lactate, implying that potentiates L-lactate-mediated astrocyte-neuron interaction. Dendritic spine density and synaptogenesis are increased in the hippocampus of Tg mice, which exhibit enhanced responses to sensory stimuli and improved performance on complex memory tasks. Hence, likely contributed to human brain evolution by enhancing synaptic plasticity and metabolic processes central to cognitive functions.
人类大脑的特征是突触传递上调，主要是谷氨酸能传递，但其进化起源仍不清楚。在这里，我们通过研究携带人类基因的转基因（Tg）小鼠来探讨这个基本问题，该人类基因参与谷氨酸代谢，出现在类人猿中，并与大脑扩张同时进化。我们证明，Tg小鼠在海马星形胶质细胞和CA1-CA3锥体神经元中表达人类酶。由theta波爆发刺激诱发的长时程增强（LTP）在Tg小鼠的CA3-CA1突触中显著增强，对CA1锥体神经元的膜片钳记录显示sNMDA电流增加。LTP增强被D-乳酸阻断，这意味着该基因增强了L-乳酸介导的星形胶质细胞-神经元相互作用。Tg小鼠海马中的树突棘密度和突触形成增加，它们对感觉刺激的反应增强，在复杂记忆任务中的表现也有所改善。因此，该基因可能通过增强突触可塑性和认知功能核心的代谢过程，对人类大脑进化做出了贡献。
