From ‘Frontiers in Neuroendocrinology’ (Felger and Miller, 2012)- Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise (review): ~ -
Under physiologic conditions, cytokines such as TNF-alpha and IL-1 have been shown to be involved in a number of essential brain processes such as synaptic remodeling, neurogenesis and long-term potentiation. However, in excess, inflammatory cytokines can act in the brain to affect monoamine neurotransmitter systems and behavior, and recent evidence indicates that dopamine function in the basal ganglia may be a primary target in this regard ~ -
Chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. ~ -
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 ~ -
Following an acute inflammatory stimulus, increased CNS 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 CNS 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, CNS inflammation can exert profound and protracted changes in neurotransmitter systems, neurotrophic factors, and neuronal integrity that can have negative outcomes on behavior.