Dystrophic serotonergic axons in neurodegenerative diseases

Efrain C. Azmitia, Ralph Nixon

Research output: Contribution to journalArticlepeer-review


Neurodegenerative diseases such as Parkinson's disease (PD), frontal lobe dementia (FLD) and diffuse Lewy-body dementia (DLBD) have diverse neuropathologic features. Here we report that serotonin fibers are dystrophic in the brains of individuals with these three diseases. In neuropathologically normal (control) brains (n = 3), serotonin axons immunoreactive (IR) with antibodies against the serotonin transporter (5-HTT) protein were widely distributed in cortex (entorhinal and dorsolateral prefrontal), hippocampus and rostral brainstem. 5-HTT-IR fibers-of-passage appeared thick, smooth, and unbranched in medial forebrain bundle, medial lemniscus and cortex white matter. The terminal branches were fine, highly branched and varicose in substantia nigra, hippocampus and cortical gray matter. In the diseased brains, however, 5-HTT-IR fibers in the forebrain were reduced in number and were frequently bulbous, splayed, tightly clustered and enlarged. Morphometric analysis revealed significant differences in the size distribution of the 5-HTT-IR profiles in dorsolateral prefrontal area between neurodegenerative diseases and controls. Our observations provide direct morphologic evidence for degeneration of human serotonergic axons in the brains of patients with neurodegenerative diseases despite the limited size (n = 3 slices for each region (3) from each brain (4), total slices was n = 36) and the lack of extensive clinical characterization of the analyzed cohort. This is the first report of dystrophic 5-HTT-IR axons in postmortem human tissue.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalBrain Research
StatePublished - Jun 27 2008


  • Aging
  • Degeneration
  • Entorhinal
  • Frontal lobe dementia
  • Hippocampus
  • Human
  • Lewy-body
  • Neuropathology
  • Parkinson's
  • Postmortem
  • Prefrontal
  • Substantia nigra

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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