Open Access
Docosahexaenoic acid ameliorates contextual fear memory deficits in the Tg2576 Alzheimer´s disease mouse model: cellular and molecular correlates
(MDPI, 2023) Badesso, Sara; Cartas Cejudo, Paz; Espelosín, María; Santamaría Martínez, Enrique; Cuadrado-Tejedor, Mar; García-Osta, Ana; Ciencias de la Salud; Osasun Zientziak
Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by studies in animal models showing that DHA reduces synaptic pathology and memory deficits. Different mechanisms to explain these beneficial effects have been proposed; however, the molecular pathways involved are still unknown. In this study, to unravel the main underlying molecular mechanisms activated upon DHA treatment, the effect of a high dose of DHA on cognitive function and AD pathology was analyzed in aged Tg2576 mice and their wild-type littermates. Transcriptomic analysis of mice hippocampi using RNA sequencing was subsequently performed. Our results revealed that, through an amyloid-independent mechanism, DHA enhanced memory function and increased synapse formation only in the Tg2576 mice. Likewise, the IPA analysis demonstrated that essential neuronal functions related to synaptogenesis, neuritogenesis, the branching of neurites, the density of dendritic spines and the outgrowth of axons were upregulated upon-DHA treatment in Tg2576 mice. Our results suggest that memory function in APP mice is influenced by DHA intake; therefore, a high dose of daily DHA should be tested as a dietary supplement for AD dementia prevention.
Open Access
Ultrahigh sensitive detection of tau protein as Alzheimer's biomarker via microfluidics and nanofunctionalized optical fiber sensors
(Wiley, 2022) Chiavaioli, Francesco; Santano Rivero, Desiree; Del Villar, Ignacio; Socorro Leránoz, Abián Bentor; Zhang, Xuejun; Li, Kaiwei; Santamaría Martínez, Enrique; Fernández Irigoyen, Joaquín; Baldini, Francesco; Van den Hove, Daniel L. A.; Shi, Lei; Bi, Wei; Guo, Tuan; Giannetti, Ambra; Matías Maestro, Ignacio; Institute of Smart Cities - ISC; Ingeniería Eléctrica y Electrónica; Ingeniaritza Elektrikoa eta Elektronikoa; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses displaying the highest death rate in the elderly. However, the existing AD diagnostic system remains elusive due to lack of a technology that may ensure enough sensitivity and reproducibility, detection accuracy, and specificity. Herein, a straightforward approach is reported to realize lab-on-fiber (LoF) technology for AD biomarker detection based on a D-shaped single-mode fiber combined with nanometer-scale metal-oxide film. The proposed sensing system, which permits the generation of lossy-mode resonance (LMR), remarkably increases the evanescent field of light guided through the fiber, and hence the fiber-surrounding medium interaction. Moreover, such optical sensors are highly repeatable in results and can safely be embedded into a compact and stable microfluidic system. Herein, the specific detection of Tau protein (as one of the classical AD biomarkers that is highly correlated with AD progression) in a complex biofluid with a detection limit of 10 12 M and over a wide concentration range (10 3 –10 μg mL 1 ) is successfully demonstrated. The proposed LoF biosensor is an appealing solution for rapid, sub-microliter dose and highly sensitive detection of analytes at low concentrations, hereby having the potential toward early screening and personalized medicine in AD.
Open Access
Dysregulated protein phosphorylation: a determining condition in the continuum of brain aging and Alzheimer's disease
(Wiley, 2021) Ferrer, Isidro; Andrés Benito, Pol; Ausín, Karina; Pamplona, Reinald; Río, José Antonio del; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Tau hyperphosphorylation is the first step of neurofibrillary tangle (NFT) formation. In the present study, samples of the entorhinal cortex (EC) and frontal cortex area 8 (FC) of cases with NFT pathology classified as stages I–II, III–IV, and V–VI without comorbidities, and of middle-aged (MA) individuals with no NFT pathology, were analyzed by conventional label-free and SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) to assess the (phospho)proteomes. The total number of identified dysregulated phosphoproteins was 214 in the EC, 65 of which were dysregulated at the first stages (I–II) of NFT pathology; 167 phosphoproteins were dysregulated in the FC, 81 of them at stages I–II of NFT pathology. A large percentage of dysregulated phosphoproteins were identified in the two regions and at different stages of NFT progression. The main group of dysregulated phosphoproteins was made up of components of the membranes, cytoskeleton, synapses, proteins linked to membrane transport and ion channels, and kinases. The present results show abnormal phosphorylation of proteins at the first stages of NFT pathology in the elderly (in individuals clinically considered representative of normal aging) and sporadic Alzheimer's disease (sAD). Dysregulated protein phosphorylation in the FC precedes the formation of NFTs and SPs. The most active period of dysregulated phosphorylation is at stages III–IV when a subpopulation of individuals might be clinically categorized as suffering from mild cognitive impairment which is a preceding determinant stage in the progression to dementia. Altered phosphorylation of selected proteins, carried out by activation of several kinases, may alter membrane and cytoskeletal functions, among them synaptic transmission and membrane/cytoskeleton signaling. Besides their implications in sAD, the present observations suggest a molecular substrate for 'benign' cognitive deterioration in 'normal' brain aging.

Santamaría Martínez, Enrique

Email Address

person.page.identifierURI

Birth Date

Job Title

Last Name

First Name

person.page.departamento

person.page.instituteName

ORCID

person.page.observainves

person.page.upna

Name

Filters

Author

Subject

Date

Has files

Item Type

Type

Settings

Sort By

Results per page

Search Results