Farsetti Elisa, Amato Sarah, Averna Monica, Guidolin Diego, Pedrazzi Marco, Maura Guido, Agnati Luigi Francesco, Cervetto Chiara, Marcoli Manuela
Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
Department of Experimental Medicine, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
Biomolecules. 2025 Aug 4;15(8):1122. doi: 10.3390/biom15081122.
The ability of the neuropeptide oxytocin to affect glial cell function is receiving increasing attention. We previously reported that oxytocin at a low nanomolar concentration could inhibit both astrocytic Ca signals and glutamate release. Here, we investigate the ability of oxytocin receptors to couple both inhibitory and stimulatory pathways in astrocytes, as already reported in neurons. We assessed the effects of oxytocin at concentrations ranging from low to high in the nanomolar range on intracellular Ca signals and on the glutamate release in astrocyte processes freshly prepared from the striatum of adult rats. Our main findings are as follows: oxytocin could induce dual responses in astrocyte processes, namely the inhibition and facilitation of both Ca signals and glutamate release; the inhibitory and the facilitatory response appeared dependent on activation of the G and the G pathway, respectively; both inhibitory and facilitatory responses were evoked at the same nanomolar oxytocin concentrations; and the biased agonists atosiban and carbetocin could duplicate oxytocin's inhibitory and facilitatory response, respectively. In conclusion, due to the coupling of striatal astrocytic oxytocin receptors to different transduction pathways and the dual effects on Ca signals and glutamate release, oxytocin could also play a crucial role in neuron-astrocyte bi-directional communication through a subtle regulation of striatal glutamatergic synapses. Therefore, astrocytic oxytocin receptors may offer pharmacological targets to regulate glutamatergic striatal transmission, which is potentially useful in neuropsychiatric disorders and in neurodegenerative diseases.
神经肽催产素影响神经胶质细胞功能的能力正受到越来越多的关注。我们之前报道过，低纳摩尔浓度的催产素能够抑制星形胶质细胞的钙信号和谷氨酸释放。在此，我们研究催产素受体与星形胶质细胞中抑制性和刺激性信号通路偶联的能力，正如在神经元中已有报道的那样。我们评估了纳摩尔范围内从低到高浓度的催产素对成年大鼠纹状体新鲜制备的星形胶质细胞突起内钙信号和谷氨酸释放的影响。我们的主要发现如下：催产素可在星形胶质细胞突起中诱导双重反应，即抑制和促进钙信号及谷氨酸释放；抑制性和促进性反应分别似乎依赖于G和G通路的激活；抑制性和促进性反应均在相同的纳摩尔催产素浓度下诱发；偏向性激动剂阿托西班和卡贝缩宫素可分别复制催产素的抑制性和促进性反应。总之，由于纹状体星形胶质细胞催产素受体与不同转导通路的偶联以及对钙信号和谷氨酸释放的双重作用，催产素也可能通过对纹状体谷氨酸能突触的精细调节在神经元 - 星形胶质细胞双向通讯中发挥关键作用。因此，星形胶质细胞催产素受体可能为调节谷氨酸能纹状体传递提供药理学靶点，这在神经精神疾病和神经退行性疾病中可能具有潜在用途。
