A study on cellular and molecular mechanisms of neuroinflammation, cholinergic deficits and novel cholinesterase inhibitors for the memory impairments

Aim of the research was: 1. Evaluate the modification of different intracellular transduction pathways and extracellular intercommunicating proteins as well as activation of microglia and astrocytes in animal models of neuroinflammation, normal aging and AD-related neurodegeneration that may lead to memory deficits. To this aim different animal models were used. In particular, the molecular mechanisms involved in neuron-glia intercommunication during inflammation in the hippocampus were studied using the model of LPS-induced neuroinflammation in the rat, developed by Prof. Gary Wenk. This part of the work was carried out in Wenk’s Lab, Psychology Department, Ohio State University, USA. The differential activation of MAPKs intracellular transduction pathways as well as the cellular modifications in the hippocampus during aging and AD related neurodegeneration were studied in normal aged rats and in TgCRND8 transgenic mice, an animal model of AD. This part of the work was carried out in Giovannini’s Lab, Department of Pharmacology, University of Florence, Italy. 2. Evaluate the efficacy of treatment with novel compounds on differentia inhibition of acetylcholinesterase/butyrilcholinesterase activity in the brain and on cortical acetylcholine release. These experiments were aimed at obtaining a proof of concept for the development of these compounds as possible drugs for the treatment of memory impairments in neurodegenerative diseases.