Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Program in Neuroscience, Indiana University, Bloomington, IN, 47405, USA.
Department of Molecular Pharmacology, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
Sci Rep. 2023 Jun 13;13(1):9610. doi: 10.1038/s41598-023-36710-3.
Autaptic hippocampal neurons are an architecturally simple model of neurotransmission that express several forms of cannabinoid signaling. Over the past twenty years this model has proven valuable for studies ranging from enzymatic control of endocannabinoid production and breakdown, to CB receptor structure/function, to CB signaling, understanding 'spice' (synthetic cannabinoid) pharmacology, and more. However, while studying cannabinoid signaling in these neurons, we have occasionally encountered what one might call 'interesting negatives', valid and informative findings in the context of our experimental design that, given the nature of scientific publishing, may not otherwise find their way into the scientific literature. In autaptic hippocampal neurons we have found that: (1) The fatty acid binding protein (FABP) blocker SBFI-26 does not alter CB1-mediated neuroplasticity. (2) 1-AG signals poorly relative to 2-AG in autaptic neurons. (3) Indomethacin is not a CB1 PAM in autaptic neurons. (4) The CB1-associated protein SGIP1a is not necessary for CB1 desensitization. We are presenting these negative or perplexing findings in the hope that they will prove beneficial to other laboratories and elicit fruitful discussions regarding their relevance and significance.
自突触海马神经元是一种结构简单的神经递质传递模型，表达几种形式的大麻素信号。在过去的二十年中，这种模型已经被证明对从酶控制内源性大麻素的产生和分解，到 CB 受体结构/功能，再到 CB 信号传递、理解“香料”（合成大麻素）药理学等方面的研究都很有价值。然而，在研究这些神经元中的大麻素信号传递时，我们偶尔会遇到一些人们可能称之为“有趣的否定”的情况，这些否定情况在我们的实验设计背景下是有效的和有信息意义的，但由于科学出版的性质，它们可能不会以其他方式出现在科学文献中。在自突触海马神经元中，我们发现：(1) 脂肪酸结合蛋白 (FABP) 阻断剂 SBFI-26 不会改变 CB1 介导的神经可塑性。(2) 在自突触神经元中，1-AG 的信号传递不如 2-AG。(3) 吲哚美辛在自突触神经元中不是 CB1 的 PAM。(4) CB1 相关蛋白 SGIP1a 对于 CB1 脱敏不是必需的。我们提出这些否定或令人困惑的发现，希望它们对其他实验室有益，并就其相关性和意义引发富有成效的讨论。
