Electroacupuncture stimulates hippocampal neurogenesis and modulates NGF metabolism and activity in experimental diabetic encephalopathy

Aim: Diabetic Encephalopathy (DE) affects neurogenesis of the hippocampal (HP) subgranular zone (SGZ) probably dysregulating the neurotrophic proNGF/NGF system, whose activity is regulated by the cholinergic neurotransmission from medial septum (MS). Electroacupuncture (EA) is effective in modulating proNGF/NGF balance in DE rats. We studied the effects of EA on: SGZ neurogenesis; proNGF/mNGF content in HP tissues; NGF receptors (TrkA and p75NTR) distribution and activity, in the MS. Methods: DE was induced in young adult rats by streptozotocin (STZ). One week after STZ, low-frequency EA treatment was started and repeated twice a week for 3 weeks. We analyzed in ctr, STZ and STZ+EA rats: the number of doublecortin (DCX)-positive cells in SGZ by confocal microscopy; the mNGF/proNGF in HP by ELISA; the colocalization of choline acetyltransferase (ChAT) and p75NTR or TrkA in MS by confocal microscopy; the activation of p75NTR pro-apoptotic signaling in MS by Western blot for the JNK/pospho-JNK. Results: SGZ neurogenesis, measured as number of DCX-positive cells, was decreased by STZ and normalized by EA. The STZ-alterated proNGF/mNGF ratio in HP was also normalized by EA. The number of cells immunopositive for ChAT and p75NTR or TrkA in MS were decreased after STZ, while EA restored control levels. In MS, EA counteracted the STZ increase of JNK phosphorylation, index of p75NTR-mediated pro-apoptotic activation. Conclusions: EA counteracts the effects of diabetes on hippocampal neurogenesis, apoptosis and neurotrophins metabolism. Thus, such physical therapy could be useful in contrasting the development of cellular and molecular correlates of diabetes-induced cognitive decline.