Reduced length of nodes of Ranvier and altered proteoglycan immunoreactivity in prefrontal white matter in major depressive disorder and chronically stressed rats.

Major depressive disorder (MDD) and chronic unpredictable stress (CUS) in animals feature comparable cellular and molecular disturbances that involve neurons and glial cells in gray and white matter (WM) in prefrontal brain areas. These same areas demonstrate disturbed connectivity with other brain regions in MDD and stress-related disorders. Functional connectivity ultimately depends on signal propagation along WM myelinated axons, and thus on the integrity of nodes of Ranvier (NRs) and their environment. Various glia-derived proteoglycans interact with NR axonal proteins to sustain NR function. It is unclear whether NR length and the content of associated proteoglycans is altered in prefrontal cortex (PFC) WM of human subjects with MDD and in experimentally stressed animals. The length of WM NRs in histological sections from the PFC of 10 controls and 10 MDD subjects, and from the PFC of control and CUS rats was measured. In addition, in WM of the same brain region, five proteoglycans, tenascin-R and NR protein neurofascin were immunostained or their levels measured with western blots. Analysis of covariance and t-tests were used for group comparisons. There was dramatic reduction of NR length in PFC WM in both MDD and CUS rats. Proteoglycan BRAL1 immunostaining was reduced at NRs and in overall WM of MDD subjects, as was versican in overall WM. Phosphacan immunostaining and levels were increased in both in MDD and CUS. Neurofascin immunostaining at NRs and in overall WM was significantly increased in MDD. Reduced length of NRs and increased phosphacan and neurocan in MDD and stressed animals suggest that morphological and proteoglycan changes at NRs in depression may be related to stress exposure and contribute to connectivity alterations. However, differences between MDD and CUS for some NR related markers may point to other mechanisms affecting the structure and function of NRs in MDD.

Working with private hospital midwives in Victoria, Australia to identify practice change priorities: Outcomes of a Delphi study.

OBJECTIVE/AIM: In this study, we invited midwives working at one metropolitan private hospital in Victoria, Australia to identify their workplace change needs and priorities for research. METHODS: In this two-round Delphi study, all midwifery staff within the maternity unit of a private hospital in Melbourne, Australia were invited to participate. In round one, participants joined face-to-face focus groups to put forward their ideas for workplace change and research ideas, and these data were developed into themes. In round two, participants ranked the themes in priority order. FINDINGS: The top four themes identified by this cohort of midwives were: 'Ways of working - investigating alternate ways of working to enable greater flexibility and opportunities'; 'Understanding midwifery - working with the executive team to highlight the nuances of maternity care'; 'Education - increase in staff in the education team to provide a greater presence and opportunity for education'; and 'Postnatal specific - review ways of working in postnatal areas'. KEY CONCLUSIONS: A number of priority research and change areas were identified which, if implemented, would strengthen both midwifery practice and midwife retention in this workplace. The findings will be of interest to midwife managers. Further research to evaluate the process and success of implementing the actions identified in this study would be valuable.

Synapsin-caveolin-1 gene therapy preserves neuronal and synaptic morphology and prevents neurodegeneration in a mouse model of AD.

Alzheimer's disease (AD) is the most common form of neurodegeneration and cognitive dysfunction in the elderly. Identifying molecular signals that mitigate and reverse neurodegeneration in AD may be exploited therapeutically. Transgenic AD mice (PSAPP) exhibit learning and memory deficits at 9 and 11 months, respectively, with associated decreased expression of caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein necessary for synaptic and neuroplasticity. Neuronal-targeted gene therapy using synapsin-Cav-1 cDNA (SynCav1) was delivered to the hippocampus of PSAPP mice at 3 months using adeno-associated virus serotype 9 (AAV9). Bilateral SynCav1 gene therapy was able to preserve MLRs profile, learning and memory, hippocampal dendritic arbor, synaptic ultrastructure, and axonal myelin content in 9- and 11-month PSAPP mice, independent of reducing toxic amyloid deposits and astrogliosis. Our data indicate that SynCav1 gene therapy may be an option for AD and potentially in other forms of neurodegeneration of unknown etiology.