Influence of maternal zinc supplementation on the development of autism-associated behavioural and synaptic deficits in offspring Shank3-knockout mice
Mol Brain. 2020-08-05; 13(1):
DOI: 10.1186/s13041-020-00650-0
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Vyas Y(1), Lee K(1), Jung Y(1), Montgomery JM(2).
Author information:
(1)Department of Physiology and Centre for Brain Research, Faculty of Medical and
Health Sciences, University of Auckland, Private Bag 92019, Auckland, New
Zealand.
(2)Department of Physiology and Centre for Brain Research, Faculty of Medical and
Health Sciences, University of Auckland, Private Bag 92019, Auckland, New
Zealand. .
Autism Spectrum Disorders (ASD) are characterised by deficits in social
interactions and repetitive behaviours. Multiple ASD-associated mutations have
been identified in the Shank family of proteins that play a critical role in the
structure and plasticity of glutamatergic synapses, leading to impaired synapse
function and the presentation of ASD-associated behavioural deficits in mice.
Shank proteins are highly regulated by zinc, where zinc binds the Shank SAM
domain to drive synaptic protein recruitment and synaptic maturation. Here we
have examined the influence of maternal dietary zinc supplementation during
pregnancy and lactation on the development of ASD-associated behavioural and
synaptic changes in the offspring Shank3 knockout (Shank3-/-) mice. Behavioural
and electrophysiological experiments were performed in juvenile and adult
Shank3-/- and wildtype littermate control mice born from mothers fed control
(30 ppm, ppm) or supplemented (150 ppm) dietary zinc. We observed that the
supplemented maternal zinc diet prevented ASD-associated deficits in social
interaction and normalised anxiety behaviours in Shank3-/- offspring mice. These
effects were maintained into adulthood. Repetitive grooming was also prevented in
adult Shank3-/- offspring mice. At the synaptic level, maternal zinc
supplementation altered postsynaptic NMDA receptor-mediated currents and
presynaptic function at glutamatergic synapses onto medium spiny neurons in the
cortico-striatal pathway of the Shank3-/- offspring mice. These data show that
increased maternal dietary zinc during pregnancy and lactation can alter the
development of ASD-associated changes at the synaptic and the behavioural levels,
and that zinc supplementation from the beginning of brain development can prevent
ASD-associated deficits in Shank3-/- mice long term.