The Neurochemistry of Parkinson's Disease

An overview of brain neurochemistry in Parkinson's Disease, written by guest blogger Ashley Juavinett.

Across the globe, one out of every 100 individuals over 60 are living with Parkinson's Disease (PD;  de Lau & Breteler, 2006) . In honour  of PD Awareness Month, we've decided to highlight the known neurochemistry underlying this debilitating disorder.

Connecting Symptoms to Dopaminergic Circuits

PD manifests itself in a variety of ways in different individuals, but the primary neurological marker is degenerated dopamine neurons in the substantia nigra pars compacta (SNc, Figure 1 and pink arrows in Figure 2). These neurons comprise a pathway to the  basal ganglia,  an interconnected set of structures in the core of the brain. The basal ganglia are involved in many different behavioral functions, but most notably movement. The dopamine in this pathway speaks to the subcortical brain areas responsible for initiating movement, therefore a lack of dopamine causes PD patients to have rigidity or “akinesia.” A popular treatment for PD, L-dopa, is a precursor to dopamine, and helps make up for lost dopamine neurons.


Figure 1. Diagram of the diminished dopamine neurons in the substantia nigra as seen in Parkinson’s disease. Courtesy of NIH.


Although dopamine has been the neurotransmitter of focus, there are downstream effects on other neurotransmitters such as GABA and glutamate. GABA and glutamate are inhibitory and excitatory neurotransmitters, respectively, and act in push-and-pull fashion to control neural activity. As evident in the circuitry of the basal ganglia (Figure 2), a lack of dopamine can impact subsequent GABA and glutamate pathways, and recent studies have confirmed that these brain chemicals are indeed altered.


A Closer Look at the Chemistry

To date, neuroscientists have used structural and functional techniques to assess the human brain during PD. While these techniques can give a gross overview of what is going on in different brain areas, they cannot give information at the resolution of neurons or neurotransmitters. However, in a recent study by a group at UT Austin, researchers used  microdialysis,  which involves inserting a small catheter into the brain, to investigate the roles of GABA and glutamate during memory tasks. Although it would normally be very difficult to use such an invasive technique, a common treatment for PD known as deep brain stimulation (DBS) already involves the insertion of electrodes into the subthalamic nucleus (STN) nestled in the brain. So, the researchers also implanted a microdialysis catheter, effectively allowing them to see what neurotransmitters were released and at roughly what time. During an implicit memory task, in which PD patients are often severely impaired, the researchers noted lower concentrations of GABA and glutamate than they would expect from normal patients  (Buchanan et al., 2014).  Although this study only had five subjects, it provides some preliminary evidence that abnormal concentrations of GABA and glutamate in the STN may be a marker for PD.


Involvement of GABA and glutamate

This study isn’t the first implicating lowered GABA concentration in the basal ganglia circuitry as a result of PD. An earlier study showing a significant loss of dopamine in post-mortem PD brains also reported a reduction in GABA in certain regions of the thalamus  (Gerlach et al., 1996).  In addition, electrophysiological recordings have shown that the STN in PD patients is hyperactive because it is not inhibited by GABA coming from the globus pallidus external (GPe). Ultimately, these changes in GABA would have an effect on the output of the thalamus and motor behaviors.

Glutamatergic pathways in the basal ganglia have also been on the radar, and glutamate receptors might be a useful target for PD, especially for dyskinesias that develop after the use of L-dopa  (Cenci et al., 2014).  In particular, it may be effective to disable the NR2B subunit of the NMDA glutamate receptor, which is abundant in the striatum. However, the use of glutamate antagonists as a treatment for PD is still in preliminary stages, as there appears to be negative cognitive effects of such treatment  (Nutt et al., 2008).

While much research is needed to unravel the genetic and environmental causes of PD, we can identify key neurochemical players based on what we know from affected brain regions. Dopamine has been the center of attention, but it’s likely that GABA and glutamate are also affected by PD and may need to be taken into consideration. With more research, scientists will hopefully be able to inform the development of comprehensive treatments for this complex disorder.


Related antibodies

Gene Symbol Name Cat. no. Tested Applications (Cited)
ABAT 4-aminobutyrate transaminase 11349-1-AP ELISA, WB, IHC
GABARD GABA A receptor subunit delta 15623-1-AP ELISA, WB
GABRA1 GABA A receptor subunit alpha 1 12410-1-AP ELISA, WB
GABRA3 GABA A receptor subunit alpha 3 12708-1-AP ELISA, WB
GABRA4 GABA A receptor subunit alpha 4 12979-1-AP ELISA, WB
GABRB1 GABA A receptor subunit beta 1 20183-1-AP ELISA, WB
GABRG1 GABA A receptor subunit gamma 1 12871-1-AP ELISA, WB, IHC
GABRG2 GABA A receptor subunit gamma 2 14104-1-AP ELISA, WB, IF
vGAT GABA vesicular transporter 14471-1-AP ELISA, WB (IF, IHC)
DRD1 Dopamine receptor D1 17934-1-AP ELISA, WB
DRD2 Dopamine receptor D2 55084-1-AP ELISA, WB
DRD5 Dopamine receptor D5 20310-1-AP ELISA, WB
DBH dopamine beta-monooxygenase 10777-1-AP ELISA, WB
GRIA2 Glutamate Receptor 2 11994-1-AP ELISA, WB, IHC
GLUD1 Glutamate dehydrogenase  (GDH1) 14299-1-AP ELISA, WB, IHC
GLUD2 Glutamate dehydrogenase  (GDH2) 14462-1-AP ELISA, WB, IHC, IF
GALD1 Glutamate decarboxylase-like 1 18240-1-AP ELISA, WB


Related Content

Proteintech interview with an early-career researcher: Odetta Antico

Neurodegeneration Antibodies

Neuronal Marker Antibodies

Induced pluripotent stem cells (iPSCs) and modeling neurodegenerative disease in the dish.






Pathway Posters Library

Early Career Researcher Hub


Newsletter Signup

Stay up-to-date with our latest news and events. New to Proteintech? Get 10% off your first order when you sign up.