Publications: Australian Animal Experimentation

@article{nokey,

title = {Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain},

author = {Nicholas A. Veldhuis et al },

url = {https://research.monash.edu/en/publications/sustained-endosomal-release-of-a-neurokinin-1-receptor-antagonist},

doi = {10.1016/j.biomaterials.2022.121536},

year  = {2022},

date = {2022-06-30},

urldate = {2022-06-30},

journal = {Biomaterials },

volume = {285},

abstract = {Soft polymer nanoparticles designed to disassemble and release an antagonist of the neurokinin 1 receptor (NK1R) in endosomes provide efficacious yet transient relief from chronic pain. These micellar nanoparticles are unstable and rapidly release cargo, which may limit the duration of analgesia. We examined the efficacy of stable star polymer nanostars containing the NK1R antagonist aprepitant-amine for the treatment of chronic pain in mice. Nanostars continually released cargo for 24 h, trafficked through the endosomal system, and disrupted NK1R endosomal signaling. After intrathecal injection, nanostars accumulated in endosomes of spinal neurons. Nanostar-aprepitant reversed mechanical, thermal and cold allodynia and normalized nociceptive behavior more efficaciously than free aprepitant in preclinical models of neuropathic and inflammatory pain. Analgesia was maintained for >10 h. The sustained endosomal delivery of antagonists from slow-release nanostars provides effective and long-lasting reversal of chronic pain.},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Altered amyloid precursor protein, tau-regulatory proteins, neuronal numbers and behaviour, but no tau pathology, synaptic and inflammatory changes or memory deficits, at 1 month following repetitive mild traumatic brain injury},

author = {Sydney M.A. Juan, Maria Daglas, Paul A. Adlard},

doi = {10.1111/ejn.15752},

year  = {2022},

date = {2022-06-29},

urldate = {2022-06-29},

journal = {European Journal of Neuroscience},

abstract = {Repetitive mild traumatic brain injury, commonly experienced following sports injuries, results in various secondary injury processes and is increasingly recognised as a risk factor for the development of neurodegenerative conditions such as chronic traumatic encephalopathy, which is characterised by tau pathology. We aimed to characterise the underlying pathological mechanisms that might contribute to the onset of neurodegeneration and behavioural changes in the less-explored subacute (1-month) period following single or repetitive controlled cortical impact injury (five impacts, 48 h apart) in 12-week-old male and female C57Bl6 mice. We conducted motor and cognitive testing, extensively characterised the status of tau and its regulatory proteins via western blot and quantified neuronal populations using stereology. We report that r-mTBI resulted in neurobehavioural deficits, gait impairments and anxiety-like behaviour at 1 month post-injury, effects not seen following a single injury. R-mTBI caused a significant increase in amyloid precursor protein, an increased trend towards tau phosphorylation and significant changes in kinase/phosphatase proteins that may promote a downstream increase in tau phosphorylation, but no changes in synaptic or neuroinflammatory markers. Lastly, we report neuronal loss in various brain regions following both single and repeat injuries. We demonstrate herein that repeated impacts are required to promote the initiation of a cascade of biochemical events that are consistent with the onset of neurodegeneration subacutely post-injury. Identifying the timeframe in which these changes occur and the pathological mechanisms involved will be crucial for the development of future therapeutics to prevent the onset or mitigate the progression of neurodegeneration following r-mTBI.},

note = {The Florey Institute of Neuroscience & Mental Health, The Melbourne Dementia Research Centre, the University of Melbourne.},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = { Replicating infant-specific reactive astrocyte functions in the injured adult brain},

author = {Leon Teo, Anthony G Boghdadi, Jihane Homman-Ludiye, Inaki-Carril Mundinano, William C Kwan, James A Bourne},

url = {https://pubmed.ncbi.nlm.nih.gov/34147584/},

doi = {10.1016/j.pneurobio.2021.102108},

year  = {2022},

date = {2022-06-17},

urldate = {2022-06-17},

abstract = {Infants and adults respond differently to brain injuries. Specifically, improved neuronal sparing along with reduced astrogliosis and glial scarring often observed earlier in life, likely contributes to improved long-term outcomes. Understanding the underlying mechanisms could enable the recapitulation of neuroprotective effects, observed in infants, to benefit adults after brain injuries. We reveal that in primates, Eph/ ephrin signaling contributes to age-dependent reactive astrocyte behavior. Ephrin-A5 expression on astrocytes was more protracted in adults, whereas ephrin-A1 was only expressed on infant astrocytes. Furthermore, ephrin-A5 exacerbated major hallmarks of astrocyte reactivity via EphA2 and EphA4 receptors, which was subsequently alleviated by ephrin-A1. Rather than suppressing reactivity, ephrin-A1 signaling shifted astrocytes towards GAP43+ neuroprotection, accounting for improved neuronal sparing in infants. Reintroducing ephrin-A1 after middle-aged focal ischemic injury significantly attenuated glial scarring, improved neuronal sparing and preserved circuitry. Therefore, beneficial infant mechanisms can be recapitulated in adults to improve outcomes after CNS injuries.},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Xenotransplantation of Genetically Modified Neonatal Pig Islets Cures Diabetes in Baboons},

author = {Hawthorn, WJ et al},

doi = {https://doi.org/10.3389/fimmu.2022.898948},

year  = {2022},

date = {2022-06-16},

urldate = {2023-06-16},

journal = {Frontiers in Immunology},

volume = {13},

abstract = {Xenotransplantation using porcine donors is rapidly approaching clinical applicability as an alternative therapy for treatment of many end-stage diseases including type 1 diabetes. Porcine neonatal islet cell clusters (NICC) have normalised blood sugar levels for relatively short periods in the preclinical diabetic rhesus model but have met with limited success in the stringent baboon model. Here we report that NICC from genetically modified (GM) pigs deleted for αGal and expressing the human complement regulators CD55 and CD59 can cure diabetes long-term in immunosuppressed baboons, with maximum graft survival exceeding 22 months. Five diabetic baboons were transplanted intraportally with 9,673 – 56,913 islet equivalents (IEQ) per kg recipient weight. Immunosuppression consisted of T cell depletion with an anti-CD2 mAb, tacrolimus for the first 4 months, and maintenance with belatacept and anti-CD154; no anti-inflammatory treatment or cytomegalovirus (CMV) prophylaxis/treatment was given. This protocol was well tolerated, with all recipients maintaining or gaining weight. Recipients became insulin-independent at a mean of 87 ± 43 days post-transplant and remained insulin-independent for 397 ± 174 days. Maximum graft survival was 675 days. Liver biopsies showed functional islets staining for all islet endocrine components, with no evidence of the inflammatory blood-mediated inflammatory reaction (IBMIR) and minimal leukocytic infiltration. The costimulation blockade-based immunosuppressive protocol prevented an anti-pig antibody response in all recipients. In conclusion, we demonstrate that genetic modification of the donor pig enables attenuation of early islet xenograft injury, and in conjunction with judicious immunosuppression provides excellent long-term function and graft survival in the diabetic baboon model.},

note = {Westmead Institute for Medical Research, NSW.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Topical wound anaesthesia: efficacy to mitigate piglet castration pain},

author = {Sheil, ML, Chambers, M and Sharpe, B.},

url = {https://pubmed.ncbi.nlm.nih.gov/32096229/},

doi = {doi: 10.1111/avj.12930},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Aust Vet Journal},

volume = {98},

issue = {6},

pages = {256-263},

note = {Piglets},

keywords = {piglets},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents},

author = {Bhedita J. Seewoo, Lauren A. Hennessy, Liz A. Jaeschke, Leah A. Mackie, Sarah J. Etherington, Sarah A. Dunlop, Paul E. Croarkin, and Jennifer Rodger},

doi = {10.1089/cap.2021.0100},

year  = {2022},

date = {2022-04-18},

urldate = {2022-04-18},

volume = {32},

number = {3},

abstract = {Abstract

Objective: Ongoing studies are focused on adapting transcranial magnetic stimulation (TMS) for the treatment of major depressive disorder in adolescent humans. Most protocols in adolescent humans to date have delivered daily 10 Hz prefrontal stimulation with mixed results. Novel TMS dosing strategies such as accelerated TMS have recently been considered. There are knowledge gaps related to the potential clinical and pragmatic advantages of accelerated TMS. This pilot study compared the behavioral effects of a standard daily and accelerated low-intensity TMS (LI-TMS) protocol in an adolescent murine model of depression.



Methods: Male adolescent Sprague Dawley rats were placed in transparent plexiglass tubes for 2.5 hours daily for 13 days as part of a study to validate the chronic restraint stress (CRS) protocol. Rats subsequently received 10 minutes of active or sham 10 Hz LI-TMS daily for 2 weeks (standard) or three times daily for 1 week (accelerated). Behavior was assessed using the elevated plus maze and forced swim test (FST). Hippocampal neurogenesis was assessed by injection of the thymidine analogue 5-ethynyl-2′-deoxyuridine at the end of LI-TMS treatment (2 weeks standard, 1 week accelerated), followed by postmortem histological analysis.},

note = {University of Western Australia, Perron Institute for Neurological & Translational Science, WA},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Rapid GFAP and Iba1 expression changes in the female rat brain following spinal cord injury},

author = {Mawj Mandwie, Jordan A Piper, Catherine A Gorrie, Kevin A Keay, Giuseppe Musumeci , Ghaith Al-Badri, Alessandro Castorina},

url = {https://pubmed.ncbi.nlm.nih.gov/34269213/},

year  = {2022},

date = {2022-02-17},

urldate = {2022-02-17},

note = {University of Technology Sydney},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Remodeling of lateral geniculate nucleus projections to extrastriate area MT following long-term lesions of striate cortex},

author = {Nafiseh Atapour, Katrina H Worthy, Marcello G P Rosa},

url = {https://pubmed.ncbi.nlm.nih.gov/35058366/},

doi = {10.1073/pnas.2117137119},

year  = {2022},

date = {2022-01-25},

urldate = {2022-01-25},

abstract = {Here, we report on a previously unknown form of thalamocortical plasticity observed following lesions of the primary visual area (V1) in marmoset monkeys. In primates, lateral geniculate nucleus (LGN) neurons form parallel pathways to the cortex, which are characterized by the expression of different calcium-binding proteins. LGN projections to the middle temporal (MT) area only originate in the koniocellular layers, where many neurons express calbindin. In contrast, projections to V1 also originate in the magnocellular and parvocellular layers, where neurons express parvalbumin but not calbindin. Our results demonstrate that this specificity is disrupted following long-term (1 to 3 y) unilateral V1 lesions, indicating active rearrangement of the geniculocortical circuit. In lesioned animals, retrograde tracing revealed MT-projecting neurons scattered throughout the lesion projection zone (LPZ, the sector of the LGN that underwent retrograde degeneration following a V1 lesion). Many of the MT-projecting neurons had large cell bodies and were located outside the koniocellular layers. Furthermore, we found that a large percentage of magno- and parvocellular neurons expressed calbindin in addition to the expected parvalbumin expression and that this coexpression was present in many of the MT-projecting neurons within the LPZ. These results demonstrate that V1 lesions trigger neurochemical and structural remodeling of the geniculo-extrastriate pathway, leading to the emergence of nonkoniocellular input to MT. This has potential implications for our understanding of the neurobiological bases of the residual visual abilities that survive V1 lesions, including motion perception and blindsight, and reveals targets for rehabilitation strategies to ameliorate the consequences of cortical blindness.},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Comparative brain structure and visual processing in octopus from different habitats},

author = {Chung et al., },

doi = {10.1016/j.cub.2021.10.070 },

year  = {2022},

date = {2022-01-10},

urldate = {2022-01-10},

journal = {Current Biology },

volume = {32},

pages = {97–110},

abstract = {Different ecologies and behavioural differences influence the octopus central nervous system (CNS) which remains largely unknown. The publication presents phylogenetically informed comparison between diurnal and nocturnal coastal and a deep-sea species using brain imaging techniques. },

note = {University of Queensland},

keywords = {Octopus},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Acute oral toxicity of zinc phosphide: an assessment for wildhouse mice (Musmusculus)},

author = {Hinds LA, Henry S, Van De Weyer N, Robinson F, Ruscoe WA, Brown R.},

url = {https://onlinelibrary.wiley.com/doi/epdf/10.1111/1749-4877.12666},

doi = {10.1111/1749-4877.12666},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

abstract = {Irregular plagues of house mice, Mus musculus, incur major economic impacts on agricultural production in Australia. The efficacy of zinc phosphide (ZnP), the only registered broadacre control agent for mice, is reported as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study, the sensitivity of mice (wild caught; outbred laboratory strain) was assessed using oral gavage of a range of ZnP concentrations. The estimated LD50values (72–79 mg ZnP/kg body weight)were similar for each mouse group but are significantly higher than previously reported. The willingness of mice to consume ZnP-coated grains was determined. ZnP-coated grains (50 g ZnP/kg grain) presented in the absence of alternative food were consumed and 94% of wild mice died. Mice provided with alternative food and ZnP-coated wheat grains (either 25 or 50 g ZnP/kg grain) consumed toxic and non-toxic grains, and mortality was lower(33–55%). If a sublethal amount of ZnP-coated grain was consumed, aversion occurred, mostly when alternative food was present. The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions, ZnP-coated grains coated with a new higher dose (50 g ZnP/kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. Our unambiguous findings for house mice indicate a re-assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted.},

keywords = {CSIRO, Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Suppression of Corticostriatal Circuit Activity Improves Cognitive Flexibility and Prevents Body Weight Loss in Activity-Based Anorexia in Rats},

author = {Laura K Milton, Paul N Mirabella, Erika Greaves, David C Spanswick, Maarten van den Buuse, Brian J Oldfield , Claire J Foldi },

url = {https://pubmed.ncbi.nlm.nih.gov/32892984/},

year  = {2021},

date = {2021-12-15},

urldate = {2021-12-15},

note = {Monash Biomedicine Discovery Institute, Monash University et al.

},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy},

author = {Mills, S.A, Jobling A.I., Dixon M.A., Fletcher E.L.},

url = {https://www.pnas.org/doi/10.1073/pnas.2112561118},

year  = {2021},

date = {2021-12-13},

urldate = {2021-12-13},

note = {University of Melbourne},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Scaffold-guided bone regeneration in large volume tibial segmental defects},

author = {Jan Henkel, Flavia Medeiros Savi, Arne Berner, Stephanie Fountain, Siamak Saifzadeh, Roland Steck, Devakar R Epari, Maria A Woodruff, Mark Knackstedt, Michael A Schuetz, Dietmar W Hutmacher},

url = {https://pubmed.ncbi.nlm.nih.gov/34461285/},

doi = {10.1016/j.bone.2021.116163},

year  = {2021},

date = {2021-12-01},

note = {Queensland University of Technology},

keywords = {Sheep},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Afferent Connections of Cytoarchitectural Area 6M and Surrounding Cortex in the Marmoset: Putative Homologues of the Supplementary and Pre-supplementary Motor Areas},

author = {Bakola S, Burman KJ, Bednarek S, Chan JM, Jermakow N, Worthy KK, Majka P, Rosa MGP.},

url = {https://pubmed.ncbi.nlm.nih.gov/34255833/},

year  = {2021},

date = {2021-11-23},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Anti-Drug antibodies in pigtailed macaques receiving HIV broadly neutralising antibody PGT121},

author = {Wen Shi Lee, Arnold Reynaldi, Thakshila Amarasena, Miles P. Davenport, Matthew S. Parsons and Stephen J. Kent},

doi = {10.3389/fimmu.2021.749891},

year  = {2021},

date = {2021-11-21},

urldate = {2021-11-21},

journal = {Frontiers in Immunology},

volume = {12},

note = {University of Melbourne},

keywords = {Macaque},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Combination of human endothelial colony-forming cells and mesenchymal stromal cells exert neuroprotective effects in the growth-restricted newborn},

author = {Kirat K. Chand, Jatin Patel, S. T. Bjorkman, Seen-Ling Sim, Stephanie M. Miller, Elliot Teo, Lara Jones, Jane Sun, Paul B. Colditz, Kiarash Khosrotehrani, Julie A. Wixey},

url = {https://www.nature.com/articles/s41536-021-00185-5.pdf},

doi = {https://doi.org/10.1038/s41536-021-00185-5},

year  = {2021},

date = {2021-11-18},

urldate = {2021-11-18},

abstract = {The foetal brain is particularly vulnerable to the detrimental effects of foetal growth restriction (FGR) with subsequent abnormal neurodevelopment being common. There are no current treatments to protect the FGR newborn from lifelong neurological disorders. This study examines whether pure foetal mesenchymal stromal cells (MSC) and endothelial colony-forming cells (ECFC) from the human term placenta are neuroprotective through modulating neuroinflammation and supporting the brain vasculature. We determined that one dose of combined MSC-ECFCs (cECFC; 106 ECFC 106 MSC) on the first day of life to the newborn FGR piglet improved damaged vasculature, restored the neurovascular unit, reduced brain inflammation and improved adverse neuronal and white matter changes present in the FGR newborn piglet brain. These findings could not be reproduced using MSCs alone. These results demonstrate cECFC treatment exerts beneficial effects on multiple cellular components in the FGR brain and may act as a neuroprotectant.},

note = {University of Queensland},

keywords = {piglets},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Visual cortical area MT is required for development of the dorsal stream and associated visuomotor behaviors},

author = {Kwan, Chang, Yu, Mundinano, Fox, Homman-Ludiye, & Bourne},

url = {https://pubmed.ncbi.nlm.nih.gov/34417331/},

year  = {2021},

date = {2021-09-29},

urldate = {2021-09-29},

abstract = {https://pubmed.ncbi.nlm.nih.gov/34417331/

},

note = {Monash University},

keywords = {Marmosets, Non-human primates},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction},

author = {Fujihara, K.M. et al},

url = {https://www.science.org/doi/10.1126/sciadv.abm9427},

year  = {2021},

date = {2021-09-14},

urldate = {2021-09-14},

journal = {Science},

volume = {8},

issue = {37},

note = {Peter MacCallum Cancer Centre, Melbourne},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = { A combination of epigenetic BET and CDK9 inhibitors for treatment of human melanoma},

author = {Emran, AA. et al},

url = {https://www.jidonline.org/article/S0022-202X(21)01121-0/fulltext},

year  = {2021},

date = {2021-09-01},

note = {Centenary Institute},

keywords = {Mice},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Adolescent oxytocin administration reduces depression-like behaviour induced by early life stress in adult male and female rats},

author = {Jade L Thornton, Nicholas A Everett, Paige Webb, Anita J Turner, Jennifer L Cornish, Sarah J Baracz},

url = {https://pubmed.ncbi.nlm.nih.gov/33567331/},

doi = {10.1016/j.pnpbp.2021.110279},

year  = {2021},

date = {2021-08-30},

urldate = {2021-08-30},

abstract = {Early life stress (ELS) exposure alters brain development, increasing vulnerability for mental illness in adulthood, including depression. Despite this association, there are no approved pharmacotherapies to protect against the emergence of mental illness resulting from ELS. Recent preclinical work showed that oxytocin (OT) administration in adulthood reduced depressive-like behaviour in male rats with a history of ELS. However, the ability of an OT treatment regime in adolescence, a critical developmental window for the OT system, to prevent the expression of depressive-like behaviours following ELS has not been investigated. Therefore, the present study aimed to determine whether chronic OT administration can ameliorate the enduring effects of ELS on depressive-like behaviours in both male and female rats. Following birth, Long Evans rat pups (N = 107) underwent maternal separation (MS) for either 15 min (MS15) or 6 h (MS360) on postnatal days (PND) 1-21. During adolescence (PND 28-42), rats received a daily injection of either OT (1 mg/kg) or saline. During adulthood (PND 57 onwards), effort-related motivation was measured using a model of effortful choice (EC), while behavioural despair was measured using the forced swim test (FST). Lastly, body and organ weights were measured to examine the physiological impacts of ELS and chronic OT administration. Overall, in both sexes, MS360 increased behavioural despair yet had no impact on effort-related motivation. Importantly, adolescent OT administration prevented the MS360-induced increase in behavioural despair in both males and females. Additionally, MS360 resulted in persistent reductions in body weight in both sexes post-weaning and increased spleen weight in males and adrenal weight in females. OT treatment had no impact on body weight in either sex, but prevented the MS-induced increase in adrenal gland weight in females. Overall, these findings have important implications for using oxytocin as a preventative pharmacotherapy after ELS.},

note = {Macquarie University},

keywords = {Rats},

pubstate = {published},

tppubtype = {article}

}