TY - JOUR
T1 - A single subanaesthetic dose of the rapid-acting antidepressant S-ketamine raises presynaptic SV2A density in limbic regions of the Wistar Kyoto rat model of depression
AU - Bærentzen, Simone Larsen
AU - Waszkiewicz, Anna Lee
AU - Thomsen, Majken
AU - Knudsen, Celine Møller Rye
AU - Elfving, Betina
AU - Landau, Anne
PY - 2024
Y1 - 2024
N2 - The N-methyl-D-aspartate receptor (NMDA-R) antagonist S-ketamine has been approved as a rapid-acting antidepressant for treatment-resistant depression (TRD). The antidepressant mechanisms have not fully been elucidated; however, alterations of synaptic proteins and mechanisms may play a vital role. Here, we study the effect of a single subanaesthetic dose of 15 mg/kg S-ketamine vs saline 1 h after administration in the Wistar Kyoto rat model of depression on the density of synaptic vesicle glycoprotein 2A (SV2A) and the metabotropic glutamate receptor 5 (mGluR5) using [3H]UCB-J and [3H]MPEPγ autoradiography, respectively, compared with control Wistar Hannover rats. In a separate cohort of Wistar Kyoto rats, we investigate the transcriptional regulation of presynaptic markers Sv2a, Syn 1–3, Syt 1–3, Synaptophysin, Vamp1, 2, 5, and 7, postsynaptic markers Homer1-3, Nrg 1, Nlgn 2, Nlgn 3, Psd95, NMDA receptor subunits Nr2a, Nr2b, AMPA receptor subunits Gria1-3, GABA type A receptor-associated protein (Gabarap), glutamate metabotropic receptor subtype 5 (Grm5), and brain-derived neurotrophic factor (Bdnf) using real-time quantitative polymerase chain reaction (qPCR) in hippocampus in response to S-ketamine vs saline injection. In Wistar Kyoto rats, S-ketamine increases [3H]UCB-J binding to SV2A compared to saline-injected controls in the nucleus accumbens and dorsal and ventral hippocampus, an effect absent in the Wistar Hannover strain. No changes were observed in [3H]MPEPγ binding to mGluR5, nor in gene regulation. S-ketamine can regulate presynaptic SV2A density in brain areas relevant to depression in the Wistar Kyoto model, but not in controls, suggesting a role for SV2A in the antidepressant effects of S-ketamine.
AB - The N-methyl-D-aspartate receptor (NMDA-R) antagonist S-ketamine has been approved as a rapid-acting antidepressant for treatment-resistant depression (TRD). The antidepressant mechanisms have not fully been elucidated; however, alterations of synaptic proteins and mechanisms may play a vital role. Here, we study the effect of a single subanaesthetic dose of 15 mg/kg S-ketamine vs saline 1 h after administration in the Wistar Kyoto rat model of depression on the density of synaptic vesicle glycoprotein 2A (SV2A) and the metabotropic glutamate receptor 5 (mGluR5) using [3H]UCB-J and [3H]MPEPγ autoradiography, respectively, compared with control Wistar Hannover rats. In a separate cohort of Wistar Kyoto rats, we investigate the transcriptional regulation of presynaptic markers Sv2a, Syn 1–3, Syt 1–3, Synaptophysin, Vamp1, 2, 5, and 7, postsynaptic markers Homer1-3, Nrg 1, Nlgn 2, Nlgn 3, Psd95, NMDA receptor subunits Nr2a, Nr2b, AMPA receptor subunits Gria1-3, GABA type A receptor-associated protein (Gabarap), glutamate metabotropic receptor subtype 5 (Grm5), and brain-derived neurotrophic factor (Bdnf) using real-time quantitative polymerase chain reaction (qPCR) in hippocampus in response to S-ketamine vs saline injection. In Wistar Kyoto rats, S-ketamine increases [3H]UCB-J binding to SV2A compared to saline-injected controls in the nucleus accumbens and dorsal and ventral hippocampus, an effect absent in the Wistar Hannover strain. No changes were observed in [3H]MPEPγ binding to mGluR5, nor in gene regulation. S-ketamine can regulate presynaptic SV2A density in brain areas relevant to depression in the Wistar Kyoto model, but not in controls, suggesting a role for SV2A in the antidepressant effects of S-ketamine.
U2 - 10.1016/j.nsa.2024.104079
DO - 10.1016/j.nsa.2024.104079
M3 - Journal article
SN - 2772-4085
VL - 3
JO - Neuroscience Applied
JF - Neuroscience Applied
M1 - 104079
ER -