Dopaminergic Co-Regulation of Locomotor Development and Motor Neuron Synaptogenesis is Uncoupled by Hypoxia in Zebrafish

Son, Jong-Hyun; Stevenson, Tamara J.; Bowles, Miranda D.; Schöll, E; Bonkowsky, Joshua L.

doi:10.1523/eneuro.0355-19.2020

Cited by 5 publications

(9 citation statements)

References 59 publications

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“…We followed the previously established hypoxia protocols (Stevenson et al, 2012;Xing et al, 2015;Son et al, 2020). Briefly, embryonic zebrafish were placed in a sealed Plexiglass chamber connected via a controller that monitored and adjusted nitrogen gas flow to a desired 1% pO 2 set point in an incubator (set as 28 • C) (Figure 1A).…”

Section: Hypoxia Reagents and Hypoxia Recoverymentioning

confidence: 99%

“…Briefly, embryonic zebrafish were placed in a sealed Plexiglass chamber connected via a controller that monitored and adjusted nitrogen gas flow to a desired 1% pO 2 set point in an incubator (set as 28 • C) (Figure 1A). Previous work had demonstrated that 1% of pO2 hypoxia is non-lethal (Stevenson et al, 2012;Son et al, 2020). Since the equilibration of oxygen partial pressure in water could take several hours, we pre-equilibrated all solutions for at least 4 h before use.…”

Section: Hypoxia Reagents and Hypoxia Recoverymentioning

confidence: 99%

“…Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed on whole-mount larvae and then followed by immunohistochemistry to visualize the diencephalic DA neurons (Son et al, 2016(Son et al, , 2020. Briefly, after standard fixation of larval zebrafish with 4% of PFA and dehydration in 100% MeOH, larvae were rehydrated stepwise into PBS with 0.1% Tween 20 (PBST), permeabilized with 10 mg/ml Proteinase K in PBST at 28 • C, washed twice with PBST, re-fixed for 20 min with 4% PFA, and washed again with PBST.…”

Section: Transferase Dutp Nick-end Labeling Assay and Tyrosine Hydrox...mentioning

confidence: 99%

“…Consistent with previous studies Wullimann, 2001, 2002), our TH immunohistochemistry also showed the majority of TH + DA neurons in diencephalic areas with seven diencephalic clusters (DC), including DC1, DC2, DC3, DC4, DC5, DC6, and DC7 at 5 dpf (Figure 3A). In particular, we focused on the DC4/5 TH + neurons as they project their axons to the spinal cord and regulate the maturation of adult-like swimming during development (Lambert et al, 2012;Son et al, 2020). We observed that there was a significant decrease in the DC4/5 TH + neurons at 5 dpf in HR zebrafish (7.7 ± 0.37 in 180.11 µm × 180.11 µm × 20 µm) compared to normoxic controls [11.8 ± 0.59 in 180.11 µm × 180.11 µm × 20 µm, t(32) = 5.746. p < 0.01, Figure 3A].…”

Section: Hypoxia-recovery Does Not Fully Restore the Development Of D...mentioning

confidence: 99%

“…In particular, cerebral palsy and other disruptions of motor skills, which have an estimated prevalence in 3 to 4 per 1,000 children in the United States (Boyle et al, 2011;Van Naarden Braun et al, 2016), are associated with hypoxic-ischemic injury and prematurity. Over the past decades, many studies have revealed that developmental hypoxia disrupts multiple aspects of brain development, including cell growth, axon pathfinding, and synapse development (Stevenson et al, 2012;Sharples et al, 2014;Xing et al, 2015;Nalivaeva et al, 2018;Son et al, 2020;Brandon et al, 2022). However, the precise mechanisms of developmental hypoxia leading to disruption of the development of motor behavior, including cerebral palsy, remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish

Son

Gerenza

Bingener

et al. 2022

Front. Cell. Neurosci.

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Hypoxic injury to the developing brain increases the risk of permanent behavioral deficits, but the precise mechanisms of hypoxic injury to the developing nervous system are poorly understood. In this study, we characterized the effects of developmental hypoxia (1% pO2 from 24 to 48 h post-fertilization, hpf) on diencephalic dopaminergic (DA) neurons in larval zebrafish and the consequences on the development of swimming behavior. Hypoxia reduced the number of diencephalic DA neurons at 48 hpf. Returning zebrafish larvae to normoxia after the hypoxia (i.e., hypoxia-recovery, HR) induced reactive oxygen species (ROS) accumulation. Real-time qPCR results showed that HR caused upregulation of proapoptotic genes, including p53 and caspase3, suggesting the potential for ROS-induced cell death. With HR, we also found an increase in TUNEL-positive DA neurons, a persistent reduction in the number of diencephalic DA neurons, and disrupted swimming development and behavior. Interestingly, post-hypoxia (HR) with the antioxidant N-acetylcysteine partially restored the number of DA neurons and spontaneous swimming behavior, demonstrating potential recovery from hypoxic injury. The present study provides new insights for understanding the mechanisms responsible for motor disability due to developmental hypoxic injury.

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Section: Hypoxia Reagents and Hypoxia Recoverymentioning

confidence: 99%

Section: Hypoxia Reagents and Hypoxia Recoverymentioning

confidence: 99%

Section: Transferase Dutp Nick-end Labeling Assay and Tyrosine Hydrox...mentioning

confidence: 99%

Section: Hypoxia-recovery Does Not Fully Restore the Development Of D...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish

Son

Gerenza

Bingener

et al. 2022

Front. Cell. Neurosci.

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Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish

Liu

Zheng

et al. 2023

Environ. Sci. Technol.

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Perfluorononanoic acid (PFNA), commonly used as an alternative polyfluorinated compound (PFC) of perfluorooctanoic acid (PFOA), has been widely detected in the aquatic environment. Previous ecotoxicological and epidemiological results suggested that some neurobehavioral effects were associated with PFC exposure; however, the ecological impacts and underlying neurotoxicity mechanisms remain unclear, particularly in aquatic organisms during sensitive, early developmental stages. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of PFNA for 120 h, and the neurological effects of PFNA were comprehensively assessed using transcriptional, biochemical, morphological, and behavioral assays. RNA sequencing and advanced bioinformatics analyses predicted and characterized the key biological processes and pathways affected by PFNA exposure, which included the synaptogenesis signaling pathway, neurotransmitter synapse, and CREB signaling in neurons. Neurotransmitter levels (acetylcholine, glutamate, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and noradrenaline) were significantly decreased in zebrafish larvae, and the Tg(gad67:GFP) transgenic line revealed a decreased number of GABAergic neurons in PFNA-treated larvae. Moreover, the swimming distance, rotation frequency, and activity degree were also significantly affected by PFNA, linking molecular-level changes to behavioral consequences.

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Development of CRID3-Based Anti-inflammatory Agents to Ameliorate Chronic Hypoxia-Induced Memory Impairment in Zebrafish Models

Soren,

Bollikanda,

Das

et al. 2024

ACS Chem. Neurosci.

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Chronic hypoxic exposure triggers the onset and progression of cognitive dysfunction; however, the mechanisms underlying chronic hypoxia-induced neuroinflammation and its contribution to cognitive dysfunction remain poorly understood. Although inflammation and hypoxia are interdependent, numerous recent studies have linked the development of various human diseases to hypoxia-induced inflammation. In this study, we focused on the NLRP3 inflammasome with novel analogues of cytokine release inhibitory drug 3 (CRID3), a class of small molecule inhibitors for the NLRP3 inflammasome, to investigate their potential contribution to alleviating chronic hypoxia-induced neuroinflammation using the zebrafish model. The designed CRID3 analogues 6a−q were prepared from 2-methyl furan-3-carboxylate, following a fourstep reaction sequence and fully characterized by NMR and mass spectral analysis. The administration of CRID3 analogues 6a−q led to a notable reduction in neuroinflammation and an increase in glial proliferation markers in both sexes. In addition, we investigated the potential effects of CRID3 analogues 6a−q through various behavioral tasks to assess their role in ameliorating post-hypoxic behavioral deficits and cognitive impairment. Notably, the study revealed that post-chronic hypoxia, male zebrafish exhibited significantly higher levels of inflammatory marker expression than females. Furthermore, we observed that the neurogenic response to treatment with CRID3 derivative 6o varied depending on the sex, with females showing a sex-specific differential increase in neurogenesis compared to males. This work emphasizes the significance of considering sex differences into account in developing therapeutic strategies for neurological disorders, as shown by the sex-specific molecular and behavioral changes in zebrafish cognitive impairment and neuroinflammation.

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Dopaminergic Co-Regulation of Locomotor Development and Motor Neuron Synaptogenesis is Uncoupled by Hypoxia in Zebrafish

Cited by 5 publications

References 59 publications

Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish

Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish

Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish

Development of CRID3-Based Anti-inflammatory Agents to Ameliorate Chronic Hypoxia-Induced Memory Impairment in Zebrafish Models

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