Towards an Understanding of the Cognitive Changes in Parkinson's

Cognitive changes are increasingly being recognised as part of the many facets of the complex condition called Parkinson’s. The basic science of which parts of the brain are changed in Parkinson’s are not well understood. There is much scientific debate about which regions are involved in the cognitive changes that occur in some people with Parkinson’s. One main area of interest is the hippocampus. It is a part of the brain that looks like a sea horse. It is heavily involved the integration of information to long term memory. The hippocampus was once considered a homogeneous structure, but increasing evidence points to the existence of differences in gene expression, function, and anatomy along its dorso-ventral axis (from top to bottom).

What do we know about the functional differences between the sub-regions of the hippocampus?  Several studies pointed out that the dorsal (top) is more related to different types of memory and cognitive functions, and the ventral (bottom) part is more associated with stress, including depression and anxiety, emotion and reward. The bottom of the hippocampus contains a larger density of dopamine terminals, and this could explain why it handles functions such  as emotion and reward. To date, few studies have investigated the consequences of reduced dopamine in the hippocampus. As far as we know, no other group had studied before how a lack of dopamine affects each region in hippocampus. We wondered how a toxin induced dopamine cell damage impactsthe top and bottom of the hippocampus. We found that loss of dopamine mainly affected the bottom region of the hippocampus. In our study, the loss of dopamine caused synaptic activity in the hippocampus to decrease over time resulting in the hippocampus attempting to compensate by generating new, but dysfunctional synapses. This change in function is commonly thought of as the cause of changes in memory.

How does dopamine loss occur in the hippocampus? Most people know that the dopamine cells are located in a brain area called substantia nigra, but fewer people have heard of another region called the ventral tegmental area (VTA).  The neurons of the VTA are also lost in Parkinsons. The loss of the VTA results in a depletion in dopamine in regions of the hippocampus.

In our study we tested whether  an existing compound called pramipexole would restore function to the hippocampus. We found that it did even after long-term damage. Treatment with pramipexole partly restored normal synaptic transmission and a produced a long term increase in the strength of nerve impulses. This data suggests a new mechanism to explain some of the actions of pramipexole in Parkinson´s disease. This is  a new mechanism that could be explored to address the design of new drugs to fight the cognitive decline and mood disorders associated with PD.

References:

Consumer information:

1)  http://www.parkinsonsvic.org.au/parkinsons-and-you/dementia-and-cognitive-change/

2)  http://www.pdf.org/en/cognitive_impairment_pd

3) The highly technical article by Castro-Hernández, Adlard and Finkelstein can be found at:   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349604/pdf/srep44426.pdf

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Professor David Finkelstein presented at the WPC 2016. He is a Professor at the Florey Institute, University of Melbourne, Australia

Dr. Castro-Hernández is currently a professor at Universidad de La Laguna , Canary Islands, Spain.

 Ideas and opinions expressed in this post reflect that of the authors solely. They do not reflect the opinions or positions of the World Parkinson Coalition®.