Genetic variants associated with neurodegenerative Alzheimer disease in natural models

The use of transgenic models for the study of neurodegenerative diseases has made valuable contributions to the field. However, some important limitations, including protein overexpression and general systemic compensation for the missing genes, has caused researchers to seek natural models that show the main biomarkers of neurodegenerative diseases during aging. Here we review some of these models-most of them rodents, focusing especially on the genetic variations in biomarkers for Alzheimer diseases, in order to explain their relationships with variants associated with the occurrence of the disease in humans.

On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae)

Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social experiences that might influence impaired cognitive abilities and the onset and progression of neurodegenerative disorders such as Alzheimer disease. We consequently suggest neuroecological approaches to examine how key elements of the environment may affect neural and cognitive mechanisms associated with learning, memory processes and brain structures involved in social behavior. We propose the following three core objectives of a program comprising interdisciplinary research in O. degus, namely: (1) to determine whether diet types provided after weaning can lead to cognitive impairment associated with spatial memory, learning and predisposing to develop Alzheimer disease in younger ages; (2) to examine if early life social experience has long term effects on behavior and cognitive responses and risk for development Alzheimer disease in later life and (3) To determine if an increase of social interactions in adult degu reared in different degree of social stressful conditions alter their behavior and cognitive responses.

Densidad neuronal en la corteza visual primaria (área 17), en dos especies de octodon / Neuronal density in primary visual cortex (17 visual area), in two species of octodon

Estudios experimentales demuestran que modificaciones medioambientales pueden producir alteraciones en el desarrollo normal de la corteza cerebral visual y sus conexiones. Por otra parte, es posible que en condiciones naturales, las especies animales hayan desarrollado adaptaciones genéticas a las distintas condiciones de luminosidad en que realizan su actividad. Recientemente, se han observado variaciones significativas en la densidad neuronal cortical del área 17 (área visual primaria), en roedores silvestres con diferentes períodos diarios de actividad y relación filogenética distante (Abrothrix olivaceus y Phyllotis darwini), pero aún no se ha determinado la naturaleza genética o plástica de dichas diferencias. En este trabajo se compararon especies con una mayor cercanía filogenética, para disminuir al máximo la variable taxonómica. Se estudió la corteza visual primaria (área 17), de roedores silvestres nativos, de las especies Octodon degus (n=5) y Octodon bridgesi (n=3), pertenecientes a la Familia Octodontidae, con el propósito de evidenciar cambios a través de la medición de la densidad neuronal, mediante la técnica del disector óptico, en cortes de 40 µm, incluidos en celoidina y teñidos con Nissl. Complementariamente, se realizó una cuantificación de la densidad neuronal de la corteza motora de las especies en estudio. O. degus, que presenta un período de actividad diurna, evidenció una densidad neuronal menor en la corteza visual (34,32 +/- 2,51 x 104 neuronas/mm3), que la observada en O. bridgesi (39,55 +/- 0,64 x 104 neuronas/mm3), especie de período de actividad nocturna; lo cual fue estadísticamente significativo (t=3,44; p<0,05). Las diferencias encontradas se podrían relacionar con el tipo de condiciones de luminosidad en que se desenvuelven dichas especies, aunque no se puede descartar la influencia de otros factores.

Studies show that environmental modifications can produce profound alterations in the normal development of the visual cortex and its connectivity. For the other hand it is possible that in natural conditions, animal species have developed genetic adaptations to the different conditions of luminance in which they normally behave. Recently have observed significant changes in cortical neuronal density of area 17 (primary visual area), in two sympatric Chilean rodents with different daily activity (Phyllotis darwini and Abrothrix olivaceus), but have not yet determined the genetic nature or plastic such differences. In this paper we compared species with a closer phylogenetic relation so as to minimize the taxonomic variable. We studied the primary visual cortex (area 17) of wild rodents native of the species Octodon degus (n=5) and Octodon bridgesi (n=3), belonging to the Octodontidae family, in order to show changes in the neuronal density, using celloidin-embedded, 40µm-thickness Nissl sections, with the aid of an optical dissector. In addition, we performed a quantification of the neuronal density of the motor cortex of the species under study. O. degus, bearing a crepuscular-diurnal activity pattern, showed a lower neuronal density in the visual cortex (34.32 +/- 2.51 x10(4) neuron/mm³) than that observed in O. bridgesi (39.55 +/- 0.64 x10(4) neuron/mm³), a species that exhibits a nocturnal phase preference, which was statistically significant (t=3.44; p<0.05). These differences might be related to differences in daily activity in two species, but we cannot discount the influence of other factors.