Electroacupuncture Ameliorates Cognitive Impairment by Regulating γ-Amino Butyric Acidergic Interneurons in the Hippocampus of 5 Familial Alzheimer's Disease Mice

Abstract

Objectives: γ-amino butyric acid (GABA)-ergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease (AD). Inhibitory interneurons play an important role in the regulation of E/I balance, synaptic transmission, and network oscillation through manipulation of GABAergic functions, showing positive outcomes in AD animal models. Mice expressing 5 familial AD mutation (5xFAD) exhibited a series of AD-like pathology and learning and memory deficits with age. Because electroacupuncture (EA) treatment has been used for a complementary alternative medicine therapy in patients with AD, we aimed to examine any usefulness of EA therapy in GABA interneuron function and its associated synaptic proteins, to determine whether EA could effectively improve inhibitory transmission and network oscillation and eventually alleviate cognitive impairments in 5xFAD mice, and to further elucidate the GABAergic system function underlying the antidementia response of EA.

Materials and methods: 5xFAD mice were used to evaluate the potential neuroprotective effect of electroacupuncture at Baihui (DU 20) and Dazhui (DU 14) through behavioral testing, immunofluorescence staining, electrophysiology recording, and molecular biology analysis.

Results: First, we observed that EA improved memory deficits and inhibitory synaptic protein expression. Second, EA treatment alleviated the decrease of somatostatin-positive interneurons in the dorsal hippocampus. Third, EA attenuated E/I imbalance in 5xFAD mice. Last, EA treatment enhanced theta and gamma oscillation in the hippocampus of 5xFAD mice.

Conclusions: EA stimulation at DU20 and DU14 acupoints may be a potential alternative therapy to ameliorate cognitive deficits in AD through the regulation of the function of the GABAergic interneuron.

Keywords: 2 Hz stimulation; Alzheimer’s disease; electroacupuncture; interneurons.