Destabilization of cortical dendrites and spines by BDNF

Particle-mediated gene transfer and two-photon microscopy were used to monitor the behavior of dendrites of individual cortical pyramidal neurons coexpressing green fluorescent protein (GFP) and brain-derived neurotrophic factor (BDNF). While the dendrites and spines of neurons expressing GFP alone grew modestly over 24-48 hr, coexpressing BDNF elicited dramatic sprouting of basal dendrites, accompanied by a regression of dendritic spines. Compared to GFP-transfected controls, the newly formed dendrites and spines were highly unstable. Experiments utilizing Trk receptor bodies, K252a, and overexpression of nerve growth factor (NGF) demonstrated that these effects were mediated by secreted BDNF interacting with extracellular TrkB receptors. Thus, BDNF induces structural instability in dendrites and spines, which, when restricted to particular portions of a dendritic arbor, may help translate activity patterns into specific morphological changes

Zinc Signal in Brain Diseases

The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer’s disease or negative outcomes following brain injury

Copper is altered across the time course.

<p>Cu revealed ipsilateral significant increases at days 7 in ROI 1 (*<i>p</i><0.01), ROI 2 (*<i>p</i><0.01), and the entire hemisphere (*<i>p</i><0.01) for trehalose treated mice. Contralateral assessment revealed significant increases at days 7 in ROI 3 (*<i>p</i><0.01) and day 7 in the entire hemisphere (*<i>p</i><0.01).</p

Trehalose treated mice show significantly enhanced willingness to explore in the open field activity test.

<p>Post-TBI treated mice showed a significant reduction in anxiety and an increased willingness to explore when compared to SSV littermates. Post-treated mice showed a significant increase in ambulatory time (****<i>p</i>< 0.00001) (a), ambulatory distance (*<i>p</i>< 0.01) (b), vertical counts (*<i>p</i>< 0.01) (c) without a significant increase in velocity (d).</p

Trehalose improves performance in the Morris water maze.

<p>Mice treated post-injury with trehalose revealed an overall significant performance improvement (two-way repeated measures ANOVA **<i>p</i> = 0.0048) in the learning (a) component of the Morris water maze. A <i>post hoc</i> Bonferroni’s multiple comparison test confirmed analysis showing significant performance of trehalose treated animals on day three (*<i>p</i> = 0.0200), day four (*<i>p</i> = 0.0197), day five (*<i>p</i> = 0.0038) and day 6 (*p = 0.0092). Trehalose treated mice also performed significantly better than SSV treated litter mates on the recall (b) component of the Morris water maze (*** <i>p</i> = 0.0010). Subsequent water maze with maltose treated and sham animals revealed no such significant improvement in the learning component of the trial. However, the recall component revealed a significantly better performance for the uninjured sham animals (ANOVA **<i>p</i> = 0.0019).</p

Trehalose treatment improves y-maze performance in TBI mice.

<p>Trehalose treated mice showed a significant overall frequency of visitation preference for the novel arm (red) over the start arm (black) compared to SSV treated littermates at both one-minute (a) (**<i>p</i>< 0.001), and five-minute frequency (b) time points (*<i>p</i>< 0.01). Additionally, trehalose treated mice spent a significantly greater duration of time in the novel arm at the one-minute (c) (**<i>p</i>< 0.001) time point when compared to SSV controls. Subsequent y-maze revealed that maltose treated mice had no significant preference for the novel arm at both the one-minute (d) or five-minute (e) frequency measurements when compared to SSV treated littermates. Similarly, the one-minute duration measurement for maltose also revealed no significant increase in the duration time of visits when compared to SSV control littermates.</p

Iron is modulated across the time course.

<p>Fe was revealed to be significantly increased in the ipsilateral cortex in ROI1 at 7 days for trehalose treated mice (a) (*<i>p</i><0.01). The contralateral side revealed an increase at day 14 for trehalose treated mice in ROI1 (b) (*<i>p</i><0.01) and the entire hemisphere (h) (*<i>p</i><0.01). Ipsilateral Fe concentrations in every region surveyed were elevated regardless of treatment when compared to equivalent contralateral regions.</p

Trehalose increases synaptophysin, DCX, BDNF & Pro-BDNF in the contralateral cortex.

<p>Trehalose significantly increased synaptophysin protein in the contralateral cortex over SSV (*p<0.0221) and maltose (*p<0.0193) controls (a). Trehalose significantly increases DCX in the contralateral cortex compared to SSV (*p<0.0147) and maltose (*p<0.0123) controls (b). Trehalose also significantly increased BDNF protein in the contralateral cortex over SSV (*<i>p</i><0.0296) and maltose (*<i>p</i><0.0255) controls (c). Trehalose significantly increased Pro-BDNF protein in the contralateral cortex over SSV (*<i>p</i><0.0210) and maltose (*<i>p</i><0.0287) controls (d).</p