Attenuation of postoperative cognitive dysfunction by Mongolian medical warm acupuncture associates with suppressed...

Postoperative cognitive dysfunction (POCD) is a common complication following surgery, characterized by hippocampus-dependent cognitive impairment as its core clinical feature. Mongolian Medical Warm Acupuncture (MMWA), a traditional therapeutic modality in Mongolian medicine, has been shown to both inhibit neuroinflammation and positively regulate neuronal migration and synaptic plasticity in various brain injury models. However, systematic evidence remains lacking as to whether these multifaceted effects are coordinated via a core upstream signaling node. MMWA was found to improve behavioral performance (including learning, memory, and spatial recognition) in POCD mice, to attenuate hippocampal neuronal damage, and to suppress pro-inflammatory cytokine levels, thereby mitigating neuroinflammation and delaying disease progression. Through analyses at the protein and transcript levels, combined with immunohistochemical staining and Golgi staining, it was revealed that MMWA restored aberrant synaptic architecture, a finding that coincided with alterations in the synaptic transmission-related protein TENM3 and associated neurotransmitter profiles. To further characterize the signaling events accompanying these phenotypic improvements, the dynamic changes of components within the PI3K/AKT and MAPK/ERK pathways (as identified by proteomic profiling) were examined. Following MMWA treatment, the phosphorylation levels of PI3K and AKT were significantly elevated, whereas the phosphorylation level of MEK was significantly reduced. In conclusion, the present study demonstrates that MMWA attenuates postoperative cognitive decline via suppressing neuroinflammation, restraining microglial activation, and preserving synaptic structural plasticity. These protective effects are accompanied by an upregulation of TENM3 and concurrent alterations in inflammation-associated signaling molecules. These findings identify TENM3 as a previously unrecognized molecular correlate underlying the neuroprotective response to MMWA in the context of POCD.