Peripheral substance P induces deficits in hippocampal synaptic plasticity and memory

Area of Science:

• Neuroscience
• Molecular Biology
• Cognitive Science

Background:

• Substance P (SP) is a neuropeptide involved in nervous system functions.
• Peripheral SP's effects on hippocampal memory remain largely unknown.
• SP can cross the blood-brain barrier.

Purpose of the Study:

• To investigate the impact of elevated peripheral Substance P on hippocampal memory and synaptic function.
• To explore the underlying molecular mechanisms.

Main Methods:

• Male mice received subcutaneous SP injections for 14 days.
• Hippocampus-dependent memory was assessed using object place and novel object recognition tests.
• Long-term potentiation (LTP) at the CA3-CA1 synapse was measured.
• Transcriptomic analysis was performed to identify differentially expressed genes.

Main Results:

• SP-treated mice showed significant deficits in hippocampus-dependent memory.
• Reduced LTP was observed at the hippocampal CA3-CA1 synapse.
• Transcriptomic analysis revealed 77 differentially expressed genes linked to synaptic transmission, learning, and memory.

Conclusions:

• Peripheral SP elevation negatively affects hippocampal memory and synaptic plasticity.
• A novel skin-brain neuropeptide signaling axis is proposed.
• Targeting peripheral SP may offer a therapeutic strategy for cognitive dysfunction linked to peripheral inflammation.