Rationale: Diabetic encephalopathy (DE) affects the function of brain cholinergic circuits1-3 and dysregulates the neurotrophic proNGF/NGF system1,3. Electroacupuncture (EA) modulates NGF and NGF receptors expression in an animal model of DE1. Objectives: To study, in experimental DE, EA effects on: long-term potentiation (LTP) in the dentate gyrus (DG); proNGF/NGF release in the hippocampus (HP); p75 neurotropin receptor (p75NTR) challenge by proNGF. Materials and Methods: DE was induced in young adult rats by streptozotocin (STZ). One week after STZ injection, EA (burst frequency of 2 Hz, intensity 1.0-1.5 mA) was started and repeated twice a week for 3 weeks. At the end of the treatments, HP tissues were collected. In HP slices from control, STZ and STZ/EA rats, we analyzed field excitatory post-synaptic potentials and LTP in the DG after electrical stimulation of the medial perforant path and proNGF isoforms release in the HP slices superfused and stimulated by the muscarinic agonist carbachol (CCh). In HP tissues we studied: the proNGF/NGF content by Western blot and ELISA4 and the role of different proNGF isoform in challenging the pro-apoptotic p75NTR by co-immunoprecipitation experiments. Results: STZ depressed and EA normalized the perforant pathway-mediated LTP. proNGF increased in diabetic rats and EA normalized pro-neurotrophin content in whole HP lysates. In superfusates, proNGF increased after CCh in STZ rats and the release was sustained over 60 minutes after stimulation. EA decreased basal proNGF release and counteracted the sustained release. The enhancement of p75NTR interaction with the 25 kDa proNGF in diabetic brain was counteracted by EA. Conclusions: EA in DE rats is effective in restoring synaptic plasticity in brain areas that produce and release proNGF. Diabetes affects and EA normalizes the production and release of proNGF, suggesting a possible mechanism based on the ability of EA to modulate the activity of the cholinergic brain.
Electroacupuncture improves hippocampal long-term potentiation and pro-nerve growth factor release and activity in a rat model of diabetic encephalopathy.
Marzia Soligo;Virginia Protto;Luigi Manni
2015
Abstract
Rationale: Diabetic encephalopathy (DE) affects the function of brain cholinergic circuits1-3 and dysregulates the neurotrophic proNGF/NGF system1,3. Electroacupuncture (EA) modulates NGF and NGF receptors expression in an animal model of DE1. Objectives: To study, in experimental DE, EA effects on: long-term potentiation (LTP) in the dentate gyrus (DG); proNGF/NGF release in the hippocampus (HP); p75 neurotropin receptor (p75NTR) challenge by proNGF. Materials and Methods: DE was induced in young adult rats by streptozotocin (STZ). One week after STZ injection, EA (burst frequency of 2 Hz, intensity 1.0-1.5 mA) was started and repeated twice a week for 3 weeks. At the end of the treatments, HP tissues were collected. In HP slices from control, STZ and STZ/EA rats, we analyzed field excitatory post-synaptic potentials and LTP in the DG after electrical stimulation of the medial perforant path and proNGF isoforms release in the HP slices superfused and stimulated by the muscarinic agonist carbachol (CCh). In HP tissues we studied: the proNGF/NGF content by Western blot and ELISA4 and the role of different proNGF isoform in challenging the pro-apoptotic p75NTR by co-immunoprecipitation experiments. Results: STZ depressed and EA normalized the perforant pathway-mediated LTP. proNGF increased in diabetic rats and EA normalized pro-neurotrophin content in whole HP lysates. In superfusates, proNGF increased after CCh in STZ rats and the release was sustained over 60 minutes after stimulation. EA decreased basal proNGF release and counteracted the sustained release. The enhancement of p75NTR interaction with the 25 kDa proNGF in diabetic brain was counteracted by EA. Conclusions: EA in DE rats is effective in restoring synaptic plasticity in brain areas that produce and release proNGF. Diabetes affects and EA normalizes the production and release of proNGF, suggesting a possible mechanism based on the ability of EA to modulate the activity of the cholinergic brain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
