a-simple-approach-to-induce-experimental-autoimmune-neuritis-c57bl6

A Simple Approach to Induce Experimental Autoimmune Neuritis in C57BL/6 Mice for Functional and Neuropathological Assessments

Experimental autoimmune neuritis (EAN) is a well-appreciated experimental model of autoimmune peripheral demyelinating diseases. EAN disease is induced by ...

The University of Melbourne

Retinitis pigmentosa refers to a family of hereditary retinal degenerations that lead to photoreceptor death and vision loss. The underlying cause(s) are not known. In recent years there has been accumulating evidence of neurochemical changes during degeneration. In particular, the amino acids glutamate, GABA, and glycine show alterations in labelling intensity in subsets of neurons. Furthermore, there are differences in the labelling of the precursors, glutamine and aspartate, prior to, during, and following loss of photoreceptors, suggesting that the metabolic pathways involved in neurotransmitter formation and degradation may be abnormal. In addition, there is an elevation in glutamine and arginine content within Müller cells prior to the onset of photoreceptor death. Investigations evaluating Müller cell function indicate that formation and degradation of glutamate, in particular, is abnormal in the degenerating retina from an early age. These studies suggest that even though the primary genetic defect of the RCS rat is within the retinal pigment epithelium, Müller cells develop abnormally, and may contribute to the observed photoreceptor loss.

Alterations in neurochemistry during retinal degeneration.

Although hormone replacement therapy (HRT) use has been associated with breast cancers that have better prognostic features, it is not clear whether this leads to improved survival. We studied a cohort of 4022 postmenopausal women diagnosed with breast cancer between 1993 and 2000, who attended a mammographic screening program, among whom 312 deaths subsequently occurred. Proportional hazards models were used to examine survival from breast cancer and all-causes among HRT users and non-users. The multivariate hazard ratio for HRT use was 0.64 (95% CI: 0.41-1.00) for breast cancer deaths and 0.69 (95% CI: 0.49-0.96) for all-cause mortality. This was attenuated by grade (HR 0.71; 95% CI: 0.45-1.10). HRT use at diagnosis was associated with modestly improved survival from breast cancer that appeared in part to be explained by the influence of HRT on tumour grade, although we cannot exclude the possibility of confounding by factors associated with the choice to use HRT.

Use of hormone replacement therapy (HRT) and survival following breast cancer diagnosis.

To examine whether there was a reduction in demand for psychological services provided through the Access to Allied Psychological Services (ATAPS) projects after the introduction of the Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule (Better Access) program, and whether any such reduction was greater in urban than rural areas.

Meeting demand for psychological services for people with depression and anxiety: recent developments in primary mental health care.

This paper reports on a multi-component evaluation of Australia's Mental Health Professionals Network (MHPN). MHPN aims to improve consumer outcomes by fostering a collaborative clinical approach to primary mental health care. MHPN has promoted interdisciplinary communication and networking through activity in three inter-related areas: interdisciplinary workshops supported by education and training materials; fostering ongoing, self-sustained interdisciplinary clinical networks; and a website, web portal (MHPN Online) and a toll-free telephone information line. The evaluation showed that MHPN's workshops were highly successful; almost 1200 workshops were attended by 11,930 individuals from a range of mental health professions. Participants from 81% of these workshops have gone on to join ongoing, interdisciplinary networks of local providers, and MHPN is now supporting these networks in a range of innovative ways to encourage them to become self-sustaining and to improve collaborative care practices.

An evaluation of an Australian initiative designed to improve interdisciplinary collaboration in primary mental health care.

Axonal damage and demyelination are major determinants of disability in patients with peripheral demyelinating neuropathies. The neurotrophin family of growth factors are essential for the normal development and myelination of the peripheral nervous system (PNS), and as such are potential therapeutic candidates for ameliorating axonal and myelin damage. In particular, BDNF promotes peripheral nerve myelination via p75 neurotrophin receptor (p75(NTR)) receptors. Here, we investigated the therapeutic efficacy of a small structural mimetic of the region of BDNF that binds to p75(NTR) (cyclo-dPAKKR) in experimental autoimmune neuritis (EAN), an established animal model of peripheral demyelinating neuropathy. Examination of rodents induced with EAN revealed that p75(NTR) is abundantly expressed in affected peripheral nerves. We found that systemic administration of cyclo-dPAKKR ameliorates EAN disease severity and accelerates recovery. Animals treated with cyclo-dPAKKR displayed significantly better motor performance compared to control animals. Histological assessment revealed that cyclo-dPAKKR administration limits the extent of inflammatory demyelination and axonal damage, and protects against the disruption of nodal architecture in affected peripheral nerves. In contrast, a structural control peptide of cyclo-dPAKKR exerted no influence. Moreover, all the beneficial effects of cyclo-dPAKKR in EAN are abrogated in p75(NTR) heterozygous mice, strongly suggesting a p75(NTR)-dependent effect. Taken together, our data demonstrate that cyclo-dPAKKR ameliorates functional and pathological defects of EAN in a p75(NTR)-dependant manner, suggesting that p75(NTR) is a therapeutic target to consider for future treatment of peripheral demyelinating diseases and targeting of p75(NTR) is a strategy worthy of further investigation.

A Brain-Derived Neurotrophic Factor-Based p75(NTR) Peptide Mimetic Ameliorates Experimental Autoimmune Neuritis Induced Axonal Pathology and Demyelination.

Sugar-free chewing gum containing polyols has been demonstrated to reduce caries experience in randomised controlled clinical trials. A range of polyols (mannitol, sorbitol, xylitol and maltitol) can be found in sugar-free gums and it has been claimed that they can facilitate calcium uptake into enamel subsurface lesions promoting remineralisation.

Article	Year
Alterations in neurochemistry during retinal degeneration. Microscopy research and technique\| PubMed ID: 10891873	2000
Use of hormone replacement therapy (HRT) and survival following breast cancer diagnosis. Breast (Edinburgh, Scotland)\| PubMed ID: 15927828	2005
Meeting demand for psychological services for people with depression and anxiety: recent developments in primary mental health care. The Medical journal of Australia\| PubMed ID: 18558908	2008
An evaluation of an Australian initiative designed to improve interdisciplinary collaboration in primary mental health care. Evaluation and program planning\| PubMed ID: 24698982	2014
A Brain-Derived Neurotrophic Factor-Based p75(NTR) Peptide Mimetic Ameliorates Experimental Autoimmune Neuritis Induced Axonal Pathology and Demyelination. eNeuro\| PubMed ID: 28680965	2017
Polyols and remineralisation of enamel subsurface lesions. Journal of dentistry\| PubMed ID: 28838679	2017

Jessica L. Fletcher

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