Long-term variable photoperiod exposure impairs hippocampal synapse involving of the glutamate system and leads to memory deficits in male Wistar rats

Abstract

Excessive artificial light at night can induce the human circadian misalignment, potentially impairing memory consolidation and the rhythms of hippocampal clock genes. To investigate the impact of circadian misalignment on hippocampal function, we measured various field excitatory postsynaptic potentials (fEPSP) and golgi staining in the CA1 and dentate gyrus (DG) regions in Wistar rats. Our findings revealed that circadian misalignment resulted in a leftward shift in the input-output (I-O) curve within the CA1 region, decreased long-term potentiation (LTP), multi-time interval paired-pulse ratio (PPR), as well as dendritic spines and complexity across both CA1 and DG regions. Additionally, magnetic resonance spectroscopy (MRS) showed that circadian misalignment downregulated glutamate-related neurotransmitters (Glu + Gln) in the hippocampus, contributing to impaired synaptic function. Furthermore, disruptions to glutamate receptor subunits due to circadian misalignment led to reduced expression of AMPA receptor and NMDA receptor subunits in the hippocampus. In summary, our results suggest that memory impairments resulting from circadian misalignment are associated with diminished functionality within the glutamatergic system; this includes reductions in both Glx levels and availability of glutamate receptor subunits—key factors contributing to compromised synaptic function within the hippocampus.