Role of proNGF and effects of electroacupuncture in the septo-hippocampal system of diabetic rats

Diabetic encephalopathy (DE) is a mild cognitive impairment associated with neurodegeneration of the cholinergic septo-hippocampal system (SHS), impaired hippocampal (HP) neurogenesis and dysregulated proNGF/NGF activity. The sensory stimulation elicited by electroacupuncture (EA) affects HP physiology and SHS neurotransmission, conceivably modulating the proNGF expression, release and activity. Here we investigated the effects of experimental type-1 diabetes and of EA on the SHS, focusing on the role of proNGF in modulating the cholinergic system and HP physiology. Twice-a-week EA treatment counteracted the diabetes-induced loss of cholinergic markers in septal neurons and their fibers; impairment in NGF/proNGF ratio; unbalance in proNGF-A/proNGF-B gene expression and protein content; impairment of hippocampal cell proliferation and differentiation into neuronal precursors. To investigate the involvement of proNGF-A and proNGF-B in the pathogenesis of DE, we delivered the two proteins intranasally in control and diabetic rats. ProNGF-B administration negatively affected the cholinergic phenotype and the hippocampal neurogenesis, while proNGF-A promoted a recovery of the diabetes-impaired cholinergic neurotransmission and improved the hippocampal neurogenesis. Our data indicate that EA could restore the diabetes-induced dysfunctions in the SHS, probably acting on the balance between the proNGF variants, which could differentially affect the development and progression of DE.