Regulation of calpain 1 and calpain 2 activity by dopamine in rat brain regions

Calpains are involved in regulating various brain functions. Limited proteolysis regulates cell proliferation, apoptosis, synaptic plasticity, long-term potentiation, and cell signaling. These are only some of the processes regulated by calpains. The current study reveals previously unexplored states of calpain activation associated with disorders of the dopaminergic system, including both hyperfunctional and hypofunctional states. In addition, activation of calpain 1 and calpain 2 affects the functioning of the central nervous system differently. Thus, this work aimed to study the effect of dopamine deficiency or excess on the activity of calpain 1 and calpain 2 in various parts of the central nervous system. We used L-dopa administration and DAT-KO rats to model a hyperdopaminergic state, and AMPT and reserpine to model a hypodopaminergic state. Dopamine deficiency causes: increased activity of calpain 1 in the striatum after AMPT administration; decreased activity of calpain 2 in the hippocampus after L-dopa administration. Excess dopamine causes: increased activity of calpains 1 and 2 in the striatum after L-dopa administration; decreased activity of calpains 1 and 2 in the midbrain after reserpine administration. Our data show that DAT knockout is associated with increased dopamine levels and increased activity of calpain 2 in the hippocampus, as well as decreased dopamine levels in the striatum and in the midbrain, accompanied by increased calpain 1 activity in the striatum.