Recovery of hippocampal functions and modulation of muscarinic response by electroacupuncture in young diabetic rats

Sci Rep. 2017 Aug 22;7(1):9077. doi: 10.1038/s41598-017-08556-z.

Abstract

The muscarinic receptor response to acetylcholine regulates the hippocampal-related learning, memory, neural plasticity and the production and processing of the pro-nerve growth factor (proNGF) by hippocampal cells. The development and progression of diabetes generate a mild cognitive impairment reducing the functions of the septo-hippocampal cholinergic circuitry, depressing neural plasticity and inducing proNGF accumulation in the brain. Here we demonstrate, in a rat model of early type-1 diabetes, that a physical therapy, the electroacupuncture, counteracts the diabetes-induced deleterious effects on hippocampal physiology by ameliorating hippocampal-related memory functions; recovering the impaired long-term potentiation at the dentate gyrus (DG-LTP) and the lowered expression of the vesicular glutamate transporter 1; normalizing the activity-dependent release of proNGF in diabetic rat hippocampus. Electroacupuncture exerted its therapeutic effects by regulating the expression and activity of M1- and M2-acetylcholine muscarinic receptors subtypes in the dentate gyrus of hippocampus. Our results suggest that a physical therapy based on repetitive sensory stimulation could promote hippocampal neural activity, neuronal metabolism and functions, and conceivably improve the diabetes-induced cognitive impairment. Our data can support the setup of therapeutic protocols based on a better integration between physical therapies and pharmacology for the cure of diabetes-associated neurodegeneration and possibly for Alzheimer's disease.

MeSH terms

  • Animals
  • Cell Count
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / physiopathology
  • Diabetes Mellitus, Experimental
  • Electroacupuncture*
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology*
  • Long-Term Potentiation
  • Memory
  • Models, Biological
  • Muscarine / metabolism*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Neuronal Plasticity
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Rats
  • Receptor, Muscarinic M1 / metabolism
  • Receptor, Muscarinic M2 / metabolism
  • Receptors, Muscarinic / metabolism

Substances

  • Nerve Growth Factors
  • Protein Precursors
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • pro-nerve growth factor, rat
  • Muscarine