Objective: To analyze the age-associated changes in the neurotransmitter/co-transmitter expression and morphometric profiles of human locus coeruleus (LC) neurons using autopsied human tissues.

Background: LC plays a significant role in both Parkinson’s disease (PD) and Alzheimer’s disease. As per the Braak staging of PD, LC pathology is associated with stage-2. Besides, the extent of pathology may differ in the individuals/populations prone to the disease. Earlier studies from our lab have reported preserved counts of melanized nigral neurons and sub-threshold neurodegeneration in the aging Asian Indians compared to the Caucasians. Therefore, the current study involves in-depth analysis of LC neurons.

Method: The tissues examined extended from the level of cerebral aqueduct to the full extent of the fourth ventricle. The number, volume and density of LC neurons were determined using the optical fractionator sampling design and nucleator probe using 40X magnification on a StereoInvestigator workstation (n=18). Every 20^th section, (n= 8-14 sections; total 200-250 sections/specimen) were quantified along the rostro-caudal extent. Secondly, immunostaining for tyrosine hydroxylase (TH) and galanin (Gal) were performed on serial sections wherein, the neuronal clusters were split into medial (MED) and lateral (LAT) groups based on their proximity to the ventricle. The neuronal diameter and expression of enzyme/neuropeptide were assessed on high magnification images using a ‘Windows’ based image analysis system (n=13). Pearson’s correlation coefficient was used to assess the age-related changes.

Results: A significant reduction in the LC volume was observed on both sides (left, r=-.51; p=0.03), (right, r=-.52; p=0.02). No changes were seen in neuronal numbers based on size/pigmentation; and density per unit area. Further, no correlation was noted in both TH- and Gal expression with age.

Conclusion: Current findings of preserved neurotransmitter/co-transmitter expression and neuronal counts in the LC match well with the previous findings on the nigra of aging Asian Indians.  The volumetric decline with age may suggest sub-threshold changes. Further, analysis of protein aggregates and autophagy may provide vital leads for relevance of LC in neurodegeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-neurotransmitter-and-co-transmitter-expression-in-the-aging-human-locus-coeruleus-relevance-to-neurodegenerative-disorders/