Synucleins deficiency alter dopamine- and glutamate-induced calcium signal in neurons and astrocytes

Proteins α-, β-, and γ-synuclein in brain distributed predominantly in presynaptic terminals suggesting their role in regulating neurotransmitter release and signal transduction. Misfolded α-synuclein is involved in the pathology of Parkinson's disease which is characterized by the loss of dopaminergic neurons and the resulting dopamine deficiency. The role of synucleins in the physiology of dopamine-controlled signal transmission is still not fully understood. Using acute brain slices from transgenic mice with α-, β-, γ-synuclein knockout (KO) we studied the effect of synuclein deficiency on dopamine and glutamate-induced calcium signals in neurons and astrocytes. We have found that lack of α- or γ -synuclein decreases the dopamine-induced calcium signal in neurons while γ- or αβγ-KO were characterized by a lower calcium signal in response to glutamate. The ability of dopamine to reduce glutamate-induced calcium signal were altered by γ- and αβγ-synuclein deficiency. Monoamine oxidase-dependent dopamine-induced calcium signal in astrocytes was increased in α-synuclein KO brain slices. αβγ-synuclein deficiency had no effect on mitochondrial Ca2+-transport and only γ-synuclein KO led to decrease in the rate of mitochondrial calcium uptake and mitochondrial calcium capacity. Thus, synuclein deficiency alters dopamine- and glutamate -induced calcium signalling in neurons and astrocytes.