Dopamine Receptors Gene Expression Pattern and Locomotor Improvement Differ Between Female and Male Zebrafish During Spinal Cord Auto Repair.

The dopaminergic system, a spinal cord (SC) motor circuit regulator, is administrated by sexual hormones and evolutionary conserved in all vertebrates. Accordingly, we hypothesized that the dopamine receptor (DAR) expression pattern may be dissimilar in female and male zebrafish SC auto repair. We implemented an uncomplicated method to induce spinal cord injury (SCI) on fully reproductive adult zebrafish, in both genders. SCI was induced using a 28-gauge needle at 9th-10th vertebra without skin incision. Thereupon, lesioned SC was harvested for DAR gene expression analysis; zebrafish were tracked routinely for any improvement in swim distance, speed, and their roaming capabilities/preference. Our findings revealed discrepancies between drd2a, drd2b, drd3, drd4a, and drd4b expression patterns at 1, 7, and 14 days postinjury (DPI) between female and male zebrafish. The receptors were mostly upregulated at 7 DPI in both genders, whereas drd2a and drd2b were mostly maximized in females. Surprisingly, drd3 was measured greater even in intact SC in males. In addition, female zebrafish were able to swim farther distances more accelerated, in multiple directions, by engaging more caudal muscles compared with males, of course with no statistical significance. Indeed, females were able to generate whole-body rotation and move forward using the muscles downstream to the lesion site, whereas the coordinated movement in males was accomplished by rostral muscles. In conclusion, there are differences in DAR gene expression pattern throughout SC autonomous recovery between adult female and male zebrafish, and also, female locomotion seems to ameliorate more rapidly.

[1]  J. Guest,et al.  Characterizing Natural Recovery after Traumatic Spinal Cord Injury. , 2020, Journal of neurotrauma.

[2]  Cody A. Siciliano,et al.  Sex differences in dopamine release regulation in the striatum , 2020, Neuropsychopharmacology.

[3]  E. Yaksi,et al.  Past, present and future of zebrafish in epilepsy research , 2021, The FEBS journal.

[4]  W. Schulze,et al.  High-resolution mapping of injury-site dependent functional recovery in a single axon in zebrafish , 2020, Communications Biology.

[5]  K. Poss,et al.  Building bridges, not walls: spinal cord regeneration in zebrafish , 2020, Disease Models & Mechanisms.

[6]  T. Becker,et al.  Dynamic cell interactions allow spinal cord regeneration in zebrafish , 2020, Current Opinion in Physiology.

[7]  R. Tyndale,et al.  Sex difference in dopamine D1-D2 receptor complex expression and signaling affects depression- and anxiety-like behaviors , 2020, Biology of Sex Differences.

[8]  P. Kaeser,et al.  Mechanisms and regulation of dopamine release , 2019, Current Opinion in Neurobiology.

[9]  L. Saúde,et al.  A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals , 2019, Scientific Reports.

[10]  Méadhbh B. Brosnan,et al.  Dopamine restores cognitive motivation in Parkinson’s disease , 2019, Brain : a journal of neurology.

[11]  P. Vidal,et al.  Targeting the Dopaminergic System in Autoimmunity , 2019, Journal of Neuroimmune Pharmacology.

[12]  Joaquim J. Ferreira,et al.  Zebrafish as an Animal Model for Drug Discovery in Parkinson’s Disease and Other Movement Disorders: A Systematic Review , 2018, Front. Neurol..

[13]  A. Kalueff,et al.  The developing utility of zebrafish models of neurological and neuropsychiatric disorders: A critical review , 2018, Experimental Neurology.

[14]  Catherina G. Becker,et al.  Reduce, reuse, recycle - Developmental signals in spinal cord regeneration. , 2017, Developmental biology.

[15]  L. Xing,et al.  Dopamine D1 receptor activation regulates the expression of the estrogen synthesis gene aromatase B in radial glial cells , 2015, Front. Neurosci..

[16]  D. McLean,et al.  Neuromodulation: Letting Sources of Spinal Dopamine Speak for Themselves , 2015, Current Biology.

[17]  C. P. Ford The role of D2-autoreceptors in regulating dopamine neuron activity and transmission , 2014, Neuroscience.

[18]  M. Oudega,et al.  Temporal Profile of Endogenous Anatomical Repair and Functional Recovery following Spinal Cord Injury in Adult Zebrafish , 2014, PloS one.

[19]  Sinnakaruppan Mathavan,et al.  Genome Wide Expression Profiling during Spinal Cord Regeneration Identifies Comprehensive Cellular Responses in Zebrafish , 2014, PloS one.

[20]  S. Higashijima,et al.  Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration. , 2013, Developmental cell.

[21]  W. Ge,et al.  Gonad differentiation and puberty onset in the zebrafish: Evidence for the dependence of puberty onset on body growth but not age in females , 2013, Molecular reproduction and development.

[22]  D. Pearse,et al.  Effect of Gender on Recovery After Spinal Cord Injury , 2013, Translational Stroke Research.

[23]  C. Pasqualini,et al.  Dopamine inhibits reproduction in female zebrafish (Danio rerio) via three pituitary D2 receptor subtypes. , 2013, Endocrinology.

[24]  J. Simmers,et al.  Opposing modulatory effects of D1- and D2-like receptor activation on a spinal central pattern generator. , 2012, Journal of neurophysiology.

[25]  Olaf Ronneberger,et al.  Comprehensive catecholaminergic projectome analysis reveals single-neuron integration of zebrafish ascending and descending dopaminergic systems , 2011, Nature communications.

[26]  Anindita Dutta,et al.  Cellular response after crush injury in adult zebrafish spinal cord , 2010, Developmental dynamics : an official publication of the American Association of Anatomists.

[27]  S. Lamberts,et al.  Novel insights in dopamine receptor physiology. , 2007, European journal of endocrinology.

[28]  T. Becker,et al.  Model Organisms in Spinal Cord Regeneration , 2006 .

[29]  Bruce R. Johnson,et al.  Dopamine modulation of phasing of activity in a rhythmic motor network: contribution of synaptic and intrinsic modulatory actions. , 2005, Journal of neurophysiology.

[30]  B. Thisse,et al.  Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[31]  J. Seamans,et al.  Dopamine Receptor Signaling , 2004, Journal of receptor and signal transduction research.

[32]  Laura L. Carruth,et al.  Sex chromosome genes directly affect brain sexual differentiation , 2002, Nature Neuroscience.

[33]  F. Gonon,et al.  Inhibition of Dopamine Release Via Presynaptic D2 Receptors: Time Course and Functional Characteristics In Vivo , 2001, The Journal of Neuroscience.