Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration.

Ascending monoaminergic systems alterations in Alzheimer's disease. translating basic science into clinical care.

Extensive neuropathological studies have established a compelling link between abnormalities in structure and function of subcortical monoaminergic (MA-ergic) systems and the pathophysiology of Alzheimer's disease (AD). The main cell populations of these systems including the locus coeruleus, the raphe nuclei, and the tuberomamillary nucleus undergo significant degeneration in AD, thereby depriving the hippocampal and cortical neurons from their critical modulatory influence. These studies have been complemented by genome wide association studies linking polymorphisms in key genes involved in the MA-ergic systems and particular behavioral abnormalities in AD. Importantly, several recent studies have shown that improvement of the MA-ergic systems can both restore cognitive function and reduce AD-related pathology in animal models of neurodegeneration. This review aims to explore the link between abnormalities in the MA-ergic systems and AD symptomatology as well as the therapeutic strategies targeting these systems. Furthermore, we will examine possible mechanisms behind basic vulnerability of MA-ergic neurons in AD.

Sensory discrimination of teeth and implant-supported restorations.

PURPOSE: The purpose of this study was to examine patient responses to load application on natural teeth and implants using a visual analog scale (VAS). MATERIALS AND METHODS: Ten subjects were selected from the University of Medicine and Dentistry of New Jersey patient pool who had a single implant-supported crown restoration adjacent to a natural tooth. Vibrational loads of 0.2 N, 0.4 N, and 0.6 N were applied to the tooth and implant-supported crown. The VAS was used to measure the magnitude of sensation. Patient responses were recorded in sets of five alternating paired trials and analyzed for differences in the responses to teeth and implant-supported crowns. RESULTS: Patients were able to discriminate between loads to implants and natural teeth 100% of the time (P = or < .01). The responses to loading of the implant were less strong than those to loading of the natural tooth 100% of the time (P = or < .01). However, the VAS score ratios between implant and natural tooth consistently increased with an increase in load. CONCLUSION: Although periodontal ligament receptors are lacking in the peri-implant area, patients appear to have some proprioceptive awareness of implant loading. This awareness becomes more similar to that of natural teeth as the vibrational load is increased.