The basal ganglia are key subcortical structures that regulate motivation and motor activity, and dopamine plays an essential modulatory role in basal ganglia function.
The effect of inflammatory cytokines on basal ganglia dopamine may be especially relevant to depression and fatigue as well as psychomotor disturbances and the development of neurodegenerative disorders” (Felger & Miller, 2012).
Cytokines from peripheral immune cells can access the Central Nervous System (CNS) by several mechanisms including:
1) Passage through leaky regions in the Blood-Brain-Barrier such as the circumventricular organs.
2) Activation of endothelial cells and perivascular macrophages in the cerebral vasculature to produce local inflammatory mediators such as cytokines, chemokines, prostaglandins, and nitric oxide.
3) Carrier-mediated transport of cytokines across the Blood-Brain-Barrier.
4) Local activation of peripheral nerve afferents which then relay cytokine signals to relevant brain regions, including the nucleus of the solitary tract and hypothalamus.
5) Recruitment of activated immune cells such as monocytes/macrophages and T cells from the periphery to the brain, where these cells can, in turn, produce cytokines.
Once in the Central Nervous System, peripheral inflammatory cytokines or “activated immune cells” can dramatically influence the tone of local inflammatory networks and propagate neuroinflammation by activating local production of cytokines and inflammatory signaling pathways, such as nuclear factor (NF)-kappaB, janus kinase (JAK)- signal transducer and activator of transcription (STAT)s, and mitogen-activated protein kinases.
Cytokines and their receptors are expressed in the brain at low levels during non-pathological states and are found to be fairly ubiquitous, yet this cytokine network in the brain can be rapidly mobilized in response to inflammatory stimuli.
Cytokines in the brain are produced primarily by microglia, but can also be produced by astrocytes and to some extent by neurons and oligodendrocytes.
Furthermore, endothelial cells and perivascular macrophages respond to circulating cytokines to induce expression of the prostaglandin-producing enzymes cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PGES).
Following acute inflammatory stimulus, increased central nervous system inflammation can confer protection to the brain and acute changes in neurotransmitter metabolism, including increases in monoamines such as serotonin and norepinephrine in the hypothalamus, can contribute to the induction of fever, activation of the HPA axis, and transition from an anabolic to a catabolic state.
Changes in monoamine metabolism are also believed to promote behavioral alterations including reduced locomotor activity and anhedonia that allow for shunting of energy and metabolic resources to combat infection and/or facilitate wound healing.
Therefore, cytokine signals from the periphery initially serve to inform the central nervous system of immune insult in order to prepare and protect an organism during times of sickness and injury.
In contrast, under conditions of chronic inflammation such as during chronic medical illnesses or depression, central nervous system inflammation can exert profound and protracted changes in neurotransmitter systems, neurotrophic factors, and neuronal integrity that can have negative outcomes on behavior.
Dopamine Control through psychological field kit countermeasures are the means to mitigate inflammation through lifestyle and self-mastery of one’s own behavior which in turn maintains homeostasis
Reduction of inflammation would reduce the chance of HPA axis dysfunction by allowing the body to return to baseline even at times of stress; mental health crisis; physical illness, etc
References
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