title: Spred-2 expression is associated with neural repair of injured adult zebrafish brain.
abstract: Sprouty-related protein-2 (Spred-2) is a negative regulator of extracellular signal-regulated kinases (ERK) pathway, which is important for cell proliferation, neuronal differentiation, plasticity and survival. Nevertheless, its general molecular characteristics such as gene expression patterns and potential role in neural repair in the brain remain unknown. Thus, this study aimed to characterise the expression of spred-2 in the zebrafish brain. Digoxigenin-in situ hybridization showed spred-2 mRNA-expressing cells were mainly seen in the proliferative zones such as the olfactory bulb, telencephalon, optic tectum, cerebellum, and the dorsal and ventral hypothalamus, and most of which were neuronal cells. To evaluate the potential role of spred-2 in neuro-regeneration, spred-2 gene expression was examined in the dorsal telencephalon followed by mechanical-lesion. Real-time PCR showed a significant reduction of spred-2 mRNA levels in the telencephalon on 1-day till 2-days post-lesion and gradually increased to normal levels as compared with intact. Furthermore, to confirm involvement of Spred-2 signalling in the cell proliferation after brain injury, double-labelling of spred-2 in-situ hybridization with immunofluorescence of BrdU and phosphorylated-ERK1/2 (p-ERK1/2), a downstream of Spred-2 was performed. Increase of BrdU and p-ERK1/2 immunoreactive cells suggest that a decrease in spred-2 after injury might associated with activation of the ERK pathway to stimulate cell proliferation in the adult zebrafish brain. The present study demonstrates the possible role of Spred-2 signalling in cell proliferative phase during the neural repair in the injured zebrafish brain.
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia.
authors.forename: Fei Tieng
authors.initials: FT
authors.lastname: Lim
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor, Malaysia. Electronic address: ishwar@monash.edu.
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Parhar
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001923:Brain Chemistry / Q000235:genetics; D001930:Brain Injuries / Q000235:genetics / Q000503:physiopathology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D015870:Gene Expression / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
chemical_list: D000963:Antimetabolites; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D012097:Repressor Proteins; D029961:Zebrafish Proteins; D001973:Bromodeoxyuridine
keywords: BrdU; ERK1/2; GFAP; Neuroregeneration; in situ hybridization