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1.
Mol Psychiatry ; 28(9): 3994-4010, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37833406

RESUMO

The pathogenesis of schizophrenia is believed to involve combined dysfunctions of many proteins including microtubule-associated protein 6 (MAP6) and Kv3.1 voltage-gated K+ (Kv) channel, but their relationship and functions in behavioral regulation are often not known. Here we report that MAP6 stabilizes Kv3.1 channels in parvalbumin-positive (PV+ ) fast-spiking GABAergic interneurons, regulating behavior. MAP6-/- and Kv3.1-/- mice display similar hyperactivity and avoidance reduction. Their proteins colocalize in PV+ interneurons and MAP6 deletion markedly reduces Kv3.1 protein level. We further show that two microtubule-binding modules of MAP6 bind the Kv3.1 tetramerization domain with high affinity, maintaining the channel level in both neuronal soma and axons. MAP6 knockdown by AAV-shRNA in the amygdala or the hippocampus reduces avoidance or causes hyperactivity and recognition memory deficit, respectively, through elevating projection neuron activity. Finally, knocking down Kv3.1 or disrupting the MAP6-Kv3.1 binding in these brain regions causes avoidance reduction and hyperactivity, consistent with the effects of MAP6 knockdown. Thus, disrupting this conserved cytoskeleton-membrane interaction in fast-spiking neurons causes different degrees of functional vulnerability in various neural circuits.


Assuntos
Neurônios , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Camundongos , Animais , Neurônios/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/farmacologia , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Emoções , Canais de Potássio Shaw/metabolismo
2.
ACS Appl Mater Interfaces ; 10(1): 827-834, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29260845

RESUMO

A hierarchical zeolitic imidazole framework (ZIF) combining a micropore with a mesoporous structure is desirable to enhance mass transport and gives rise to novel applications. Here, hierarchically porous graphene/ZIF-8 hybrid aerogel (GZAn) materials were successfully prepared by a two-step reduction strategy and a layer-by-layer assembly method. To avoid a tedious dry step and the use of an energy-consuming freeze-drying technology, a reduced graphene oxide hydrogel with different reduction degrees was chosen as a template to grow ZIF-8 crystals in situ. The parameter of density and elemental analysis was adopted to calculate the amount of ZIF-8 in GZAn materials for different assembly cycles. The distribution of micropores and mesopores of GZAn materials was controlled by changing the loading of ZIFs in GZAn materials. Furthermore, GZA8 materials showed enhanced CO2 uptake capacity (0.99 mmol g-1, 298 K, 1 bar) than pure ZIF-s crystals and pure graphene aerogels, showing an excellent synergistic effect of hierarchical pore structures. Meanwhile, with the increase of ZIF-8 loading, the mechanical robustness of GZAn was uplifted obviously. This work provides an efficient method to prepare hierarchically porous ZIFs-based materials with good CO2 uptake capacity and tunable mechanical robustness.

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