Articles

Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

Authors:

Abstract

Background: Dystonias (Dys) represent the third most common movement disorder after essential tremor (ET) and Parkinson’s disease (PD). While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions ofDys brains, mostly in the basal ganglia (BG), and specifically in the substantia nigra (SN). Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia) have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies.

Methods: Quantitative immunohistochemistry protocolswere used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age-matched control subjects (C).

Results: We observed a significant reduction (~20%) of pigmented neurons in the SNofDys compared to C (p<0.01). Neither significant volumetric changes nor evident neurodegenerative signswere observed in the remaining pool of nigral pigmented neurons inDys brains.These novel quantitative findingswere confirmed after exclusion of possible co-occurring SN pathologies including Lewy pathology, tau-neurofibrillary tangles, b-amyloid deposits, ubiquitin (ubiq), and phosphorylated-TARDNA-binding protein 43 (pTDP43)-positive inclusions.

Discussion: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

Keywords:

Substantia nigrapigmented neuronsneuronal reductionneuronal lossneurodevelopmental disorderneurodegenerative disorder
  • Year: 2015
  • Volume: 5
  • Page/Article: tre-5-301
  • DOI: 10.5334/tohm.241
  • Submitted on 29 Jan 2015
  • Accepted on 7 Mar 2015
  • Published on 13 May 2015
  • Peer Reviewed