Role of the Precursor Nerve Growth Factor and Effects of Electroacupuncture in an Animal Model of Diabetic Encephalopathy

The work presented in this thesis studied the impact of experimentally induced early type-1 diabetes on septo-hippocampal physiology, by analyzing the role played proNGF, and the effect of electroacupuncture in the recovery of the cholinergic phenotype and on neurogenesis as a peculiar hippocampal function. Main experimental tasks were: 1. Investigating the impairment of medial septum and hippocampal structures induced in a rat experimental model of early Type 1 Diabetes, and their rescue by electroacupuncture; 2. Studying how the tissue content of proNGF and the relative expression of its two main protein variants are affected by diabetes and modulated by electroacupuncture; 3. Studying the tissue content and distribution of NGF receptors and how they are activated by different proNGF variants; 4. Investigating the impact of diabetes and electroacupuncture on hippocampal neurogenesis; 5. Analyzing the role of different purified proNGF isoforms by studying their effects on the septo-hippocampal cholinergic phenotype and on the hippocampal neurogenesis after diabetes induction and electroacupuncture. The results indicate that, in early diabetic rats, the physical therapy (electroacupuncture) favors the maintenance of the cholinergic phenotype and of proper hippocampal neurogenesis. Electroacupuncture modulates protein expression and distribution of the neurotrophin proNGF, involved in the regulation of septo-hippocampal physiology. Main take-home message of this experimental work is the promotion of physical therapies, such as electroacupuncture, as simple and effective interventions supportive of more complex and sometimes invasive pharmacological approaches targeting central neurons for the care of neurodegenerative diseases.