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NeuroScience Associates

Parkinson Disease

Overview

The primary pathological features of Parkinson Disease (PD) in humans are the loss of dopamine cells, the presence of Lewy bodies in existing cells and changes in the expression of alpha-synuclein. Disease models vary and NSA employs a wide range of tools suited to the traits of specific models.

Rodent TissueRodent brains are the primary tissue processed in PD Research by NSA. NSA can process up to 40 tissues in each MultiBrain® Block.

25 Mouse Brains Coronal

Up to 25 mouse brains are co-embedded and appear on each MultiBrain® slide section.

16 Coronal Rat Brains

Up to 16 rat brains are co-embedded and appear on each MultiBrain® slide section.

40 Mouse or 32 rat Brain Hemispheres

Up to 40 mouse brains are co-embedded and appear on each MultiBrain® slide section.

Human Tissue:

NSA processes large format sections, as seen below, providing a unique opportunity to assess large contiguous cross-sections of tissue. NSA also processes multiple smaller samples from one or more brains using MultiBrain® Technology. The standard NSA practice of encasing the brain tissue in gelatin provides a significant aid in the handling of tissue sections resulting in an improved final product.

Human Brain Hemisphere

Multi-Embedded Human Brain Tissues

PD Endpoint: Tyrosine Hydroxylase (TH) Immunohistochemistry

PD research models typically use a method to induce the loss of dopamine cells or create lesions that interrupt the axons projecting to striatum. Tyrosine Hydroxylase is a robust marker of elements of the dopamine system.

Rat brain normal expressing TH equally in both hemispheres.

Rat animal model treated to create the loss of the dopamine cells that produce TH.

16 rat brains of a PD model on a MultiBrain® slide at the approximate same levels. All brains have lost TH staining in the left striatum.

 

Tyrosine Hydroxylase IHC

AgNOR-TH in Substantia Nigra

TH-Stained Substantia Nigra

 

 

 

 

 

AgNOR-TH in Substantia Nigra

 

A silver nucleolar stain (AgNOR: Ag Nucleolar Organizing Region protocol used in oncology research), when paired with Tyrosine Hydroxylase IHC staining, is an excellent tool for use in stereology in Parkinson research.

Alpha-Synuclein pSer129 Mouse Brain Cortex,10x

Alpha-Synuclein pSer129 Mouse Brain Cortex, 20x

Alpha-Synuclein pSer129 Synthetic A-Syn Fibril Injected  Mouse Brain Cortex, 20x

Alpha-Synuclein pSer129 A53T mouse cortex, pyramidal cells

 

 

 

Alpha-Synuclein pSer129 Substantia nigra in a human PD brain, cytoplasmic and axonal aggregates, 60x

 

Placement of a vector containing the code for human alpha-synuclein in rat brains is taken up by cells and Alpha-Synuclein is expressed.

 

 

 

Transgenic mouse brain expressing human Alpha-Synuclein 211 (121-125), 20x (left) and 40x (right)

Disintegrative Degeneration

In PD research, models that employ an acute method of destroying the TH-producing cells, the degeneration of those cells can be witnessed using a Disintegrative Degeneration stain: Cupric Silver deOlmos method.

 

 

Degenerated neurons in substantia nigra in MPTP-treated BALB/C57 mouse

Inflammation

As with other disease models, inflammation markers such as GFAP and Iba1 can be useful indicators of perturbations in conjunction with other PD pathology.

 

Aberrant Iron in PD

Iron ‘decompartmentalized’ has been implicated in the pathologic process. Useful tools for probing this include Perls-DAB for ferric iron and Ferritin IHC for the iron storage molecule.

Perls-DAB reveals iron in the substantia nigra (left) and red nucleus (right) of this human tissue. This section was counterstained for nissl substance with Thionine (blue).

If you would like further information about how NSA can assist you with your research, please contact us or refer to our catalog.