Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism.
Synucleins are involved in multiple steps of the neurotransmitter turnover, but the largely normal synaptic function in young adult animals completely lacking synucleins suggests their roles are dispensable for execution of these processes. Instead, they may be utilized for boosting the efficiency of certain molecular mechanisms in presynaptic terminals, with a deficiency of synuclein proteins sensitizing to or exacerbating synaptic malfunction caused by accumulation of mild alterations, which are commonly associated with aging. Although functional redundancy within the family has been reported, it is unclear whether the remaining synucleins can fully compensate for the deficiency of a lost family member or whether some functions are specific for a particular member. We assessed several structural and functional characteristics of the nigrostriatal system of mice lacking members of the synuclein family in every possible combination and demonstrated that stabilization of the striatal dopamine level depends on the presence of α-synuclein and cannot be compensated by other family members, whereas β-synuclein is required for efficient maintenance of animal's balance and coordination in old age.
School of Biosciences, Cardiff University, Cardiff, UK.
Natalie
N
Connor-Robson
School of Biosciences, Cardiff University, Cardiff, UK.
Owen M
OM
Peters
School of Biosciences, Cardiff University, Cardiff, UK.
Steven
S
Millership
School of Biosciences, Cardiff University, Cardiff, UK; Institute of Physiologically Active Compounds RAS, Moscow Region, Russian Federation.
Natalia
N
Ninkina
School of Biosciences, Cardiff University, Cardiff, UK; Institute of Physiologically Active Compounds RAS, Moscow Region, Russian Federation. Electronic address: buchmanvl@cf.ac.uk.
Vladimir L
VL
Buchman
D000375:Aging / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology; D004856:Postural Balance / Q000502:physiology; D013378:Substantia Nigra / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D051843:Synucleins / Q000172:deficiency* / Q000502:physiology*
D018377:Neurotransmitter Agents; D051843:Synucleins; D004298:Dopamine
Dopamine; Knockout mice; Nigrostriatal system; Null mutant; Parkinson's disease; Synuclein