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Microglial Activation

March 22, 2011

Inflammation

March 22, 2011

Altered Stress Response

March 22, 2011

Oxidation

March 22, 2011

Mitochondrial Failure

March 21, 2011

Stress Response

March 21, 2011

Although often unrecognized by Medicine, Parkinson’s patients struggle with a poorly regulated stress response. As a disruption of the endocrine system’s “fight or flight” circuitry, it becomes more and more evident as the disorder progresses. It seems more common as a problem associated with Young Onset and is generally seen as a dysregulation of the hypothalamus – pituitary – adrenal complex (the HPA axis).

When it is recognized it is often dismissed as another symptom to be papered over with anti-depressants. It is seldom accepted for what it is – one of the primary processes leading to YOPD.

In the later stages of the disorder, this disrupted stress response can become more of a problem than the motor symptoms generally thought to be the hallmarks of PD. When one looks at the broader picture presented here, several points become more and more evident-

  • Dysfunctional stress response is a defining feature of YOPD and differentiates it from Senior Onset.
  • Many of the non-motor symptoms arise from the dysregulation of the HPA.
  • The same chain of events that lead to the immune/inflammatory aspects of PD also produce this endocrine/HPA disfunction.
  • The two systems, immune and endocrine, at some point begin to interact in an amplifying feedback loop and the disorder spins out of control. This can be triggered by challenge to either system. It is common for PWP to report an immune challenge such as influenza or an endocrine challenge such as the loss of a loved one in the months just before diagnosis.

It is only by addressing this paired degenerative force that we can understand PD.

Neuroinflammation

March 21, 2011

Neuroinflammation is a bit different than “inflammation”, primarily as a result of the involvement of the immune system cells called the “microglia”.  Neuroinflammation is a condition of the central nervous system and takes place beyond the obscuring wall of the blood brain barrier. There is communication across that barrier, however, which results in the triggering of neuroinflammation by ordinary, or peripheral, inflammation.

In both immune responses, the net result is the release of cytokines, a family of communication molecules that allows for the control of that response. Some increase inflammation and some repress it.

One aspect of cytokines that is often overlooked is that they are neuroactive and give the immune system the ability to take control. This is called “sickness behavior” and is most evident when a cold or the flu sends us to our bed.

Neuroinflammation’s severity is determined by individual sensitivity and by the nature of the challenge. Individual sensitivity is determined by a number of factors, such as genetics, epigenetics, prenatal exposure to bacterial toxins, adult infection, etc.

Cytokine induced inflammation does not act alone. The endocrine system has a similar structure as the immune and produces hormones which fill the same roles of communication and coordination.

The single most important thing to realize is that both the immune and endocrine systems respond to stress and stress acts as a sort of Rosetta Stone allowing the two systems to interact with one another. This interaction ultimately triggers the synergistic actions o a feedback loop. The immune component destroys the substantia nigra with its high density of microglia. The endocrine component succumbs to the stress response and accounts for most of the non-motor symptoms.

This view of Parkinson’s Disease as a complex interaction between the endocrine and immune systems damaging the CNS is, while fragmented, supported by the existing literature.

Neuroinflammation and Influenza

Neuroinflammation – Part 1

Neuroinflammation – Part 2

Neuroinflammation – Part 3

Neuroinflammation – Part 4

Neuroinflammation – Part 5

Inflammation and Immune Factors