Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas

0581674 - ÚOCHB 2025 RIV DE eng J - Článek v odborném periodiku
Mihalj, D. - Borbélyová, V. - Pirník, Zdenko - Bacova, Z. - Ostatníková, D. - Bakos, J.
Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas.
Neurochemical Research. Roč. 49, č. 4 (2024), s. 1008-1016. ISSN 0364-3190. E-ISSN 1573-6903
Institucionální podpora: RVO:61388963
Klíčová slova: autism spectrum disorder * olfactory system * shank3 * GABAergic synapse
Impakt faktor: 4.4, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1007/s11064-023-04097-2

Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances in olfactory processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the olfactory system in ASD remains unclear. Therefore, the present study aimed to evaluate selected components of the GABAergic system in olfactory brain regions and primary olfactory neurons isolated from Shank3-deficient ((-/-)) mice, which are known for their autism-like behavioral phenotype. Shank3 deficiency led to a significant reduction in GEPHYRIN/GABA(A)R colocalization in the piriform cortex and in primary neurons isolated from the olfactory bulb, while no change of cell morphology was observed. Gene expression analysis revealed a significant reduction in the mRNA levels of GABA transporter 1 in the olfactory bulb and Collybistin in the frontal cortex of the Shank3(-/-) mice compared to WT mice. A similar trend of reduction was observed in the expression of Somatostatin in the frontal cortex of Shank3(-/-) mice. The analysis of the expression of other GABAergic neurotransmission markers did not yield statistically significant results. Overall, it appears that Shank3 deficiency leads to changes in GABAergic synapses in the brain regions that are important for olfactory information processing, which may represent basis for understanding functional impairments in autism.
Trvalý link: https://hdl.handle.net/11104/0349784