Involutive and Adaptative Cellular Mechanisms in Neurodegenerative Diseases

Work deals with the study of both the normal and the pathological involution of the Central Nervous System in order to explain the pathogeny of neurodegenerative disorders and to open new therapeutical lines. Studies are carried out in a multidisciplinary approach, using morphological, histochemical and biochemical methods. Human Alzheimer`s and Creutzfeldt-Jakob´s Diseases, sheep scrapie and experimental models of Alzheimer and CNS Oxidative Stress are mainly studied.

1. Study on peripheral blood biomarkers (amyloid peptides, oligomers, oxidative stress markers, cytokines, pro-imflamatory system markers, etc.) in humans suffering Alzheimer´s Diseases and related dementias (MCI, vascular and frontotemporal dementias, etc). Using morphological, histochemical and microspectroscopic methods blood biomarkers are studied to develop diagnostic protocols. Two international patents are being developed.

2. Study of central and peripheral biomarkers in non-human primates and experimental models of Alzheimer´s Disease (transgenic mice) using morphological and histochemical methods to understand the pathogeny of the disease and develop strategies for diagnosis and treatment.

3. Characteristics of the human cerebellar cortex during both normal –senile- and pathological -Alzheimer’s (AD), Creutzfeldt-Jakob (CJD), Familiar Fatal Imsomnia (FFI), as well as of the sheep scrapie. Morphological and histochemical alterations of both neurons and glial cells in demented (AD, CJD, FFI) and non-demented elderly people, and in sheep suffering scrapie are being studied, for detecting the first pathological changes (pro-inflammatory systems, glial reaction, neuronal apoptosis, etc.) as well as neuroprotective mechanisms (synaptic proteins, neurotrophic systems, etc.)

4. Characterization of Alzheimer experimental models obtained by lesion/dysfunction of the nucleus basalis of the white rat. Long-term evolution (three years). Alzheimer experimental models have been obtained with rats by stereotaxical unilateral injections of selected neurotoxins (ibotenic, quisqualic and NMDA acids - 7.5 to 100nmols). Both involutive and adaptative changes in the basalo-cortical cholinergic systems and cerebral cortex are being studied.

5. CNS effects of nicotine treatments in normal young and senile rats, and in Alzheimer experimental models.
Different types of CNS effects induced by nicotinic (accute and chronic treatments) in normal and experimental (mainly nbM-lesioned) rats, at different age of life, are being studied to demonstrate the therapeutic properties of the specific stimulation of the cortical nicotinic receptors in Alzheimer’s disease and other less severe cognitive disorders. Several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei, have increased after acute or chronic nicotine treatments, as well as the neuronal and/or the glial content of some neurotrophic peptides (NGF, VIP, etc.).

Most relevant methodology:

A multidisciplinary (morphological, histochemical –both at the ligt and electron microscopical level-, biochemical) approach. Image analysis and tridimensional reconstruction of normal and pathological structures.