PUBLICATION

Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior

Authors: Zhang, Q., Li, T., Lin, J., Zhang, Y., Li, F., Chen, X., Wang, X., Li, Q.
ID: ZDB-PUB-220305-9
Date: 2022
Source: iScience 25: 103876 (Journal)
Registered Authors: Li, Qiang, Wang, Xu
Keywords: Biological sciences, Developmental neuroscience, Molecular neuroscience, Transcriptomics
MeSH Terms: none
PubMed: 35243238 Full text @ iScience

Abstract

The cytoskeletal protein NDE1 plays an important role in chromosome segregation, neural precursor differentiation, and neuronal migration. Clinical studies have shown that NDE1 deficiency is associated with several neuropsychiatric disorders including autism. Here, we generated nde1 homologous deficiency zebrafish (nde1^-/- ) to elucidate the cellular molecular mechanisms behind it. nde1^-/- exhibit increased neurological apoptotic responses at early infancy, enlarged ventricles, and shrank valvula cerebelli in adult brain tissue. Behavioral analysis revealed that nde1^-/- displayed autism-like behavior traits such as increased locomotor activity and repetitive stereotype behaviors and impaired social and kin recognition behaviors. Furthermore, nde1 mRNA injection rescued apoptosis in early development, and minocycline treatment rescued impaired social behavior and overactive motor activity by inhibiting inflammatory cytokines. In this study, we revealed that nde1 homozygous deletion leads to abnormal neurological development with autism-related behavioral phenotypes and that inflammatory responses in the brain are an important molecular basis behind it.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
apoeb	nde1^{zf3784/zf3784} (TU)	standard conditions	Days 45-89	brain	RTPCR	Fig. 5
apoeb	nde1^{zf3784/zf3784} (TU)	standard conditions	Day 4	whole organism	RTPCR	Fig. 6
apoeb	TU	standard conditions	Days 45-89	brain	RTPCR	Fig. 5
apoeb	TU	standard conditions	Day 4	whole organism	RTPCR	Fig. 6
bbc3	nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6
bbc3	TU	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6
bcl2a	nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6
bcl2a	TU	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6
bcl2l1	nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6
bcl2l1	TU	standard conditions	Prim-15	whole organism	RTPCR	Fig. 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TU	chemical treatment by environment: minocycline	Adult	social behavior normal process quality, normal	Fig. 7
TU	chemical treatment by environment: minocycline	Adult	swimming behavior normal process quality, normal	Fig. 7
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	midbrain apoptotic process increased process quality, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	rhombomere apoptotic process increased process quality, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	spinal cord apoptotic process increased process quality, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	telencephalon apoptotic process increased process quality, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	whole organism bicd2 expression increased amount, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	whole organism gmnn expression increased amount, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-5	whole organism pcna expression increased amount, abnormal	Fig. 6
nde1^{zf3784/zf3784} (TU)	standard conditions	Prim-15	midbrain apoptotic process increased process quality, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
zf3784		Small Deletion	nde1

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nde1	CRISPR1-nde1	CRISPR

Fish

Fish
nde1^{zf3784/zf3784} (TU)
TU

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Zhang et al., 2022 ZDB-PUB-220305-9 PMID:35243238

Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior

Zhang et al., 2022

ZDB-PUB-220305-9
PMID:35243238