ABSTRACT
Mammalian aging is often characterized by metabolic disturbances, cognitive declines and DNA repairs deficiency, but the underlying molecular mechanisms are still not well understood. Alterations in DNA repair can significantly exacerbate aging. Mammalian neuronal cells which accumulate unrepaired DNA damage over time could potentially lead to brain functions disorders. Focusing on the ATP-dependent RecQ-type DNA helicase, an enzyme involved in repair of double strand DNA, a mouse model of Werner syndrome (WS) had been proposed as a model of accelerated aging. Until now, no study has investigated the impact of this premature aging syndrome on learning and memory. Spatial memory and cognitive flexibility are particularly affected by the aging process in both men and rodents. Studies have shown that aged mice exhibited similar performance than young adult mice on non-hippocampus dependent memory whereas their performances were decreased in hippocampus-dependent tasks. In this study, we have submitted 3, 5 and 8 month-old WS mice to several behavioral paradigms to evaluate hippocampus-dependent (spatial object location, Morris water maze and fear conditioning) and non hippocampus-dependent (object recognition) memories. No effect on the locomotion activity and anxiety level has been observed in adult WS mice. Interestingly, the 8 month-old WS mice exhibit long-term memory impairment similar to aged mice, suggesting that adult WS mice do develop some aspects of cognitive aging.
Subject(s)
Anxiety , Memory , Motor Activity , Werner Syndrome/psychology , Aging , Animals , Behavior, Animal , Conditioning, Classical , Disease Models, Animal , Fear , Female , Hippocampus , Male , Maze Learning , Mice , Mice, Inbred C57BL , Recognition, Psychology , Werner Syndrome Helicase/geneticsSubject(s)
Psychotic Disorders/complications , Werner Syndrome/complications , Atrophy , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Humans , Middle Aged , Psychomotor Agitation/psychology , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/psychology , Tomography, X-Ray Computed , Wechsler Scales , Werner Syndrome/diagnostic imaging , Werner Syndrome/psychologyABSTRACT
Werner's syndrome is a premature aging syndrome with many features common to normal aging. The possible association between phenotypic markers for normal aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins age 70-90 years. All participants were scored every second year using a number of physical and cognitive tests. In addition their self-rated health was registered as well as self reported status with regards to nine diseases. Blood was drawn from all participants and purified DNA was typed for four SNP's in the WRN gene. The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an unpaired analysis of this material a significant association between the intron 1 SNP and cognitive function was demonstrated. Our finding, which will need corroboration in independent samples, therefore may suggest that the t-allele of the intron 1 SNP is beneficial to cognitive function. However, since the t-allele of this SNP is very rare, we did not encounter any tt-homozygous individuals for this allele.
Subject(s)
Aging/genetics , Cognition , Diseases in Twins , Polymorphism, Single Nucleotide , Werner Syndrome/genetics , Activities of Daily Living , Aged , Aged, 80 and over , Aging/psychology , Female , Haplotypes , Health Status Indicators , Humans , Introns , Male , Neuropsychological Tests , Werner Syndrome/psychologyABSTRACT
The literature on Werner's syndrome is scarce, and to our knowledge, no documented evidence is available to substantiate central nervous system involvement in this multisystem disease. We present a case of Werner's syndrome associated with recurrent delusional psychosis in the presence of cognitive impairment and computerised tomography (CT) radiological changes in the posterior cerebral cortex.
