Neurobiology of aging
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Neurobiology of aging · Aug 2011
No replication of genetic association between candidate polymorphisms and Alzheimer's disease.
Alzheimer's disease is a genetically complex disorder, for which new putative susceptibility genes are constantly proposed in the literature. We selected 16 candidate genes involved in biological pathways closely related to the pathology, and for which a genetic association with Alzheimer's disease was previously detected: ACE, BACE1, BDNF, ECE1, HSPG2, IDE, IL1a, IL6, IL10, MAPT, PLAU, PrnP, PSEN1, SORL1, TFCP2 and TGFb1. The variants originally associated with the disease were genotyped in a French Caucasian sample including 428 cases and 475 controls and tested for association in order to replicate the initial results. Despite a careful replication study design, we failed to validate the initial findings for any of these variants, with the possible exception of MAPT, SORL1 and TFCP2 for which some nominal but inconsistent evidence of association was observed.
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Neurobiology of aging · Aug 2011
The wake-promoting effects of hypocretin-1 are attenuated in old rats.
Disruption of sleep is a frequent complaint among elderly humans and is also evident in aged laboratory rodents. The neurobiological bases of age-related sleep/wake disruption are unknown. Given the critical role of the hypocretins in sleep/wake regulation, we sought to determine whether the wake-promoting effect of hypocretin changes with age in Wistar rats, a strain in which age-related changes in both sleep and hypocretin signaling have been reported. ⋯ An increase of parameters associated with homeostatic sleep recovery after sleep deprivation, including non-rapid eye movement (NR) sleep time, NR delta power, the ratio of NR to rapid eye movement (REM) sleep, and NR consolidation, occurred subsequent to Hcrt-induced waking in young but not old rats. ICV infusions of hypocretin-2 (10 and 30 μg) produced fewer effects in both young and old rats. These data demonstrate that activation of a major sleep/wake regulatory pathway is attenuated in old rats.
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Neurobiology of aging · Aug 2011
Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide.
Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach for improvement of cognition in learning and memory disorders such as Alzheimer's disease. Here we report the development of an 11-mer peptide that we designed based on a biologically active region of the ciliary neurotrophic factor. This peptide, Peptide 6, induced proliferation and increased survival and maturation of neural progenitor cells into neurons in the dentate gyrus of normal adult C57BL6 mice. ⋯ Thirty-day treatment of the mice with a slow release bolus of the peptide implanted subcutaneously improved reference memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over 6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic and neurotrophic and that this peptide is effective when given peripherally, demonstrates its potential for prevention and treatment of learning and memory disorders.