Preservation of noradrenergic neurons in the locus ceruleus that coexpress galanin mRNA in Alzheimer's disease.
Galanin (GAL) innervation is hypertrophied in the basal forebrain and cortex of patients with Alzheimer's disease (AD). Increased GAL could exacerbate the cognitive and behavioral deficits of AD because GAL acts as an inhibitory modulator of cholinergic and noradren-ergic neurotransmission. The locus ceruleus (LC) may be a source of increased GAL in AD because (a) GAL is coexpressed in a subset of LC neurons, (b) GAL expression is up-regulated with neuronal injury, and (c) the LC undergoes extensive degeneration in AD. Therefore, we have used in situ hybridization histochemistry to measure GAL gene expression in the LC of AD patients and sex- and age-matched nondemented controls. Despite the extensive loss of norepinephrine neurons with AD, GAL mRNA-expressing neurons in the LC did not differ between groups. This resulted in a significant increase in the percentage of neuromelanin-pigmented cells that coexpressed GAL in AD patients compared with controls. These findings raise the possibility that the increased incidence of GAL expression among remaining LC neurons contributes to the hyperinnervation of GAL fibers in AD. Furthermore, GAL may be neuroprotective in the LC.
Miller
M A
MA
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA.
Kolb
P E
PE
Leverenz
J B
JB
Peskind
E R
ER
Raskind
M A
MA
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019004:Galanin / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008543:Melanins / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism
D008543:Melanins; D012333:RNA, Messenger; C014121:neuromelanin; D019004:Galanin; D009638:Norepinephrine