Shati/Nat8l deficiency disrupts adult neurogenesis and causes attentional impairment through dopaminergic neuronal dysfunction in the dentate gyrus | Zendy

Wulaer Bolati | Zendy; Kunisawa Kazuo | Zendy; Hada Kazuhiro | Zendy; Jaya Suento Willy | Zendy; Kubota Hisayoshi | Zendy; Iida Tsubasa | Zendy; Kosuge Aika | Zendy; Nagai Taku | Zendy; Yamada Kiyofumi | Zendy; Nitta Atsumi | Zendy; Yamamoto Yasuko | Zendy; Saito Kuniaki | Zendy; Mouri Akihiro | Zendy; Nabeshima Toshitaka | Zendy

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Shati/Nat8l deficiency disrupts adult neurogenesis and causes attentional impairment through dopaminergic neuronal dysfunction in the dentate gyrus

Author(s) -

Wulaer Bolati,

Kunisawa Kazuo,

Hada Kazuhiro,

Jaya Suento Willy,

Kubota Hisayoshi,

Iida Tsubasa,

Kosuge Aika,

Nagai Taku,

Yamada Kiyofumi,

Nitta Atsumi,

Yamamoto Yasuko,

Saito Kuniaki,

Mouri Akihiro,

Nabeshima Toshitaka

Publication year - 2021

Publication title -

journal of neurochemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.75

H-Index - 229

eISSN - 1471-4159

pISSN - 0022-3042

DOI - 10.1111/jnc.15022

Subject(s) - neurogenesis , dentate gyrus , dopamine , neuroscience , dopaminergic , hippocampus , psychology , endocrinology , medicine , biology

Successful completion of daily activities relies on the ability to select the relevant features of the environment for memory and recall. Disruption to these processes can lead to various disorders, such as attention-deficit hyperactivity disorder (ADHD). Dopamine is a neurotransmitter implicated in the regulation of several processes, including attention. In addition to the higher-order brain function, dopamine is implicated in the regulation of adult neurogenesis. Previously, we generated mice lacking Shati, an N-acetyltransferase-8-like protein on a C57BL/6J genetic background (Shati/Nat8l -/- ). These mice showed a series of changes in the dopamine system and ADHD-like behavioral phenotypes. Therefore, we hypothesized that deficiency of Shati/Nat8l would affect neurogenesis and attentional behavior in mice. We found aberrant morphology of neurons and impaired neurogenesis in the dentate gyrus of Shati/Nat8l -/- mice. Additionally, research has suggested that impaired neurogenesis might be because of the reduction of dopamine in the hippocampus. Galantamine (GAL) attenuated the attentional impairment observed in the object-based attention test via increasing the dopamine release in the hippocampus of Shati/Nat8l -/- mice. The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, and dopamine D1 receptor antagonist, SCH23390, blocked the ameliorating effect of GAL on attentional impairment in Shati/Nat8l -/- mice. These results suggest that the ameliorating effect of GAL on Shati/Nat8l -/- attentional impairment is associated with activation of D1 receptors following increased dopamine release in the hippocampus via α7 nicotinic acetylcholine receptor. In summary, Shati/Nat8l is important in both morphogenesis and neurogenesis in the dentate gyrus and attention, possible via modulation of dopaminergic transmission. Cover Image for this issue: https://doi.org/10.1111/jnc.15061.

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