Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia: Evidence of compensatory changes

Abstract In Alzheimer’s disease (AD) there is a significant loss of locus coeruleus (LC) noradrenergic neurons. However, recent work has shown the surviving noradrenergic neurons to display many compensatory changes, including axonal sprouting to the hippocampus. The prefrontal cortex (PFC) is a forebrain region that is affected in dementia, and receives innervation from the LC noradrenergic neurons. Reduced PFC function can reduce cognition and disrupt behavior. Because the PFC is an important area in AD, we determined if noradrenergic innervation from the LC noradrenergic neurons is maintained and if adrenoreceptors are altered postsynaptically. Presynaptic PFC α2 -adrenoreceptor (AR) binding site density, as determined by3 H-RX821002, suggests that axons from surviving noradrenergic neurons in the LC are sprouting to the PFC of subjects with dementia. Changes in postsynaptic α1 -AR in the PFC of subjects with dementia indicate normal to elevated levels of binding sites. Expression of α1 -AR subtypes (α1A - and α1D -AR) and α2C -AR subtype mRNA in the PFC of subjects with dementia is similar to what was observed in the hippocampus with one exception, the expression of α1A -AR mRNA. The expression of the α1A -AR mRNA subtype is significantly reduced in specific layers of the PFC in subjects with dementia. The loss of α1A -, α1D - and α2C -AR mRNA subtype expression in the PFC may be attributed to neuronal loss observed in dementia. These changes in postsynaptic AR would suggest a reduced function of the PFC. Consequence of this reduced function of the PFC in dementia is still unknown but it may affect memory and behavior.