Age-related memory decline is associated with vascular and microglial degeneration in aged rats.
The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration.
Liggins Institute, University of Auckland, Auckland, New Zealand.
Rong
R
Zhang
Tamar
T
Kadar
Ernest
E
Sirimanne
Alastair
A
MacGibbon
Jian
J
Guan
D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000150:complications* / Q000473:pathology*; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D013550:Swimming; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014652:Vascular Diseases / Q000150:complications* / Q000473:pathology; D042442:Vascular Endothelial Growth Factors
D000954:Antigens, Surface; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D042442:Vascular Endothelial Growth Factors; C114781:endothelial barrier antigen, rat; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase