15-07-08(19:08:32)
Authors:
Lockrow JP, Boger HA, Granholm AC
Institutions:
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
Title of abstract : Locus coeruleus degeneration in a mouse model for Down syndrome: A potential stimulus for neuroinflammation
Abstract text:
Individuals with Down syndrome (DS), or trisomy 21, develop the neuropathological hallmarks of Alzheimer’s disease (AD), including amyloid deposition, cholinergic neuron degeneration, and early-onset dementia. A mouse containing a partial trisomy of murine chromosome 16, the Ts65Dn mouse, expresses a triplication of many of the genes implicated in DS pathology. These mice recapitulate several of the salient features of DS, including cholinergic neuron loss and age-dependent memory dysfunction. In addition, there are indications that Ts65Dn mice exhibit attentional and anxiety-related deficits, which led us to assess morphological alterations in noradrenergic neurons of the locus coeruleus (LC) in this model. LC neurons, which project heavily to cortical and hippocampal regions and may modulate inflammatory gene expression, show premature degeneration in several neurodegenerative diseases, including DS and AD. The present study analyzed LC neurons in the Ts65Dn mouse and assessed whether changes in the LC may contribute to increases in neuroinflammation. We found a depletion of noradrenergic neurons at 10 months in Ts65Dn mice, primarily in the rostral LC. In addition, the hippocampus of Ts65Dn mice at this age exhibited morphological changes to microglia and astrocytes consistent with inflammation, as well as increased gene expression of inflammatory markers such as iNOS and COX-2. We are currently evaluating the inflammatory response to an LC lesion in Ts65Dn mice. These changes to the noradrenergic system, which appear to precede the rise of inflammation in Ts65Dn mice, may influence the progression of pathology that results in the impairment of brain function in DS.
