TY - JOUR
T1 - Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule
AU - Borcel, Erika
AU - Pérez-Alvarez, Laura
AU - Herrero, Ana Isabel
AU - Brionne, Thomas
AU - Varea, Emilio
AU - Berezin, Vladimir
AU - Bock, Elisabeth
AU - Sandi, Carmen
AU - Venero, César
N1 - Keywords: Aging; Analysis of Variance; Animals; Animals, Newborn; Bromodeoxyuridine; Cell Proliferation; Cell Survival; Chronic Disease; Dentate Gyrus; Hippocampus; Immunohistochemistry; Indicators and Reagents; Male; Maze Learning; Memory Disorders; Molecular Mimicry; Neural Cell Adhesion Molecules; Neurons; Rats; Rats, Wistar; Stress, Psychological
PY - 2008
Y1 - 2008
N2 - In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed each week to a stress stimulus. When evaluated in the water maze at the early stages of aging (18 months old), chronic unpredictable stress accelerated spatial-cognitive decline, an effect that was accompanied by a reduction in the survival of newborn cells and in the number of adult granular cells in the hippocampus. Interestingly, spatial-memory performance in the Morris water maze was positively correlated with the number of newborn cells that survived in the dentate gyrus: better spatial memory in the water maze was associated with more 5-bromo-2-deoxyuridine (BrdU)-labeled cells. Administration of FGL, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent the decrease in the total number of granular neurons that resulted from prolonged exposure to stress. These findings suggest that the development of new drugs that mimic neural cell adhesion molecule activity might be of therapeutic relevance to treat stress-induced cognitive impairment.
AB - In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed each week to a stress stimulus. When evaluated in the water maze at the early stages of aging (18 months old), chronic unpredictable stress accelerated spatial-cognitive decline, an effect that was accompanied by a reduction in the survival of newborn cells and in the number of adult granular cells in the hippocampus. Interestingly, spatial-memory performance in the Morris water maze was positively correlated with the number of newborn cells that survived in the dentate gyrus: better spatial memory in the water maze was associated with more 5-bromo-2-deoxyuridine (BrdU)-labeled cells. Administration of FGL, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent the decrease in the total number of granular neurons that resulted from prolonged exposure to stress. These findings suggest that the development of new drugs that mimic neural cell adhesion molecule activity might be of therapeutic relevance to treat stress-induced cognitive impairment.
U2 - 10.1097/FBP.0b013e3282f3fca9
DO - 10.1097/FBP.0b013e3282f3fca9
M3 - Journal article
C2 - 18195593
SN - 0955-8810
VL - 19
SP - 41
EP - 49
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 1
ER -