Immune maintenance in glaucoma: boosting the body’s own neuroprotective potential

Glaucoma, a slow progressive neurodegenerative disorder associated with death of retinal ganglion cells and degeneration of their connected optic nerve fibers, has been classically linked to high intraocular pressure. Regardless of the primary risk factor, degeneration may continue, resulting in further loss of neurons and subsequent glaucomatous damage. During the past decade, scientists and clinicians began to accept that, in addition or as an alternative to fighting off the primary risk factor(s), there is a need to protect the tissue from the ongoing spread of damage—an approach collectively termed “neuroprotection.” We found that the immune system, the body’s own defense mechanism, plays a key role in the ability of the optic nerve and the retina to withstand glaucomatous conditions. This defense involves recruitment of both innate and adaptive immune cells that together create a protective niche and thereby halt disease progression. The spontaneous immune response might not be sufficient, and therefore, we suggest boosting it by immunization (with the appropriate antigen, at specific timing and predetermined optimal dosing) which may be developed into a suitable therapeutic vaccination to treat glaucoma. This view of immune system involvement in glaucoma will raise new challenges in glaucoma research, changing the way in which clinicians perceive the disease and the approach to therapy.     

Coming to America: Acclimation in macaque body structures and Bergmann’s rule

I analyzed somatometric measurements from subsets of the Texas and Oregon transplanted troops of Japanese macaques(Macaca fuscata) to reveal secular changes in body size and shape. Body weights of the Texas population (N = 59) are lower than those of the Oregon population(N = 49) and the founding population from Arashiyama. The adult weights of the Oregon population are significantly higher than the founding population from Mihara. There are significant differences in adult circumferential measures and in skinfolds, which are correlated with the increased weight of the Oregon macaques. The adult Texas macaques have longer limb segments in comparison with the adult Oregon troop members, while the latter have significantly longer heads and trunks. Examination of the developing morphological trends through regression analyses on the complete sample suggests distinctive growth patterns for each population. Members of the Texas population start with smaller initial measurements but hold a steeper growth pattern for limb segments, while the Oregon macaques start larger in most measures and show lower growth rates. I argue that these differences in both somatometry and growth patterns are related to the differing climatic conditions under which the translocated macaques have lived. This set of analyses supports the basic arguments for Bergmann’s rule and Allen’s rule.     

Erratum to: Pathogenetic heterogeneity of restless legs syndrome in Parkinson’s disease

Sleep and Biological Rhythms -     

Equatorial sandhoppers use body scans to detect the earth’s magnetic field

Adults of Talorchestia martensii were individually released in a confined environment, with and without the natural magnetic field, under the sun and in a dark room. The sandhoppers scanned the horizontal component of the magnetic field by left and right oscillations of the entire major body axis. The frequency of this behaviour increased in a zeroed magnetic field, as did the frequencies of other behavioural indicators that reflect the difficulty in identifying the ecologically efficient orientation direction (sea–land axis). Therefore, like head scans in birds, body scans seem to be used by equatorial sandhoppers to detect the magnetic symmetry plane.     

Reactions to Media Violence: It’s in the Brain of the Beholder

Media portraying violence is part of daily exposures. The extent to which violent media exposure impacts brain and behavior has been debated. Yet there is not enough experimental data to inform this debate. We hypothesize that reaction to violent media is critically dependent on personality/trait differences between viewers, where those with the propensity for physical assault will respond to the media differently than controls. The source of the variability, we further hypothesize, is reflected in autonomic response and brain functioning that differentiate those with aggression tendencies from others. To test this hypothesis we pre-selected a group of aggressive individuals and non-aggressive controls from the normal healthy population; we documented brain, blood-pressure, and behavioral responses during resting baseline and while the groups were watching media violence and emotional media that did not portray violence. Positron Emission Tomography was used with [¹⁸F]fluoro-deoxyglucose (FDG) to image brain metabolic activity, a marker of brain function, during rest and during film viewing while blood-pressure and mood ratings were intermittently collected. Results pointed to robust resting baseline differences between groups. Aggressive individuals had lower relative glucose metabolism in the medial orbitofrontal cortex correlating with poor self-control and greater glucose metabolism in other regions of the default-mode network (DMN) where precuneus correlated with negative emotionality. These brain results were similar while watching the violent media, during which aggressive viewers reported being more Inspired and Determined and less Upset and Nervous, and also showed a progressive decline in systolic blood-pressure compared to controls. Furthermore, the blood-pressure and brain activation in orbitofrontal cortex and precuneus were differentially coupled between the groups. These results demonstrate that individual differences in trait aggression strongly couple with brain, behavioral, and autonomic reactivity to media violence which should factor into debates about the impact of media violence on the public.     

From bench to bed: the potential of stem cells for the treatment of Parkinson’s disease

Parkinson’s disease (PD) is the most common movement disorder. The neuropathology is characterized by the loss of dopamine neurons in the substantia nigra pars compacta. Transplants of fetal/embryonic midbrain tissue have exhibited some beneficial clinical effects in open-label trials. Neural grafting has, however, not become a standard treatment for several reasons. First, the supply of donor cells is limited, and therefore, surgery is accompanied by difficult logistics. Second, the extent of beneficial effects has varied in a partly unpredictable manner. Third, some patients have exhibited graft-related side effects in the form of involuntary movements. Fourth, in two major double-blind placebo-controlled trials, there was no effect of the transplants on the primary endpoints. Nevertheless, neural transplantation continues to receive a great deal of interest, and now, attention is shifting to the idea of using stem cells as starting donor material. In the context of stem cell therapy for PD, stem cells can be divided into three categories: neural stem cells, embryonic stem cells, and other tissue-specific types of stem cells, e.g., bone marrow stem cells. Each type of stem cell is associated with advantages and disadvantages. In this article, we review recent advances of stem cell research of direct relevance to clinical application in PD and highlight the pros and cons of the different sources of cells. We draw special attention to some key problems that face the translation of stem cell technology into the clinical arena.     

Biomarkers of Alzheimer’s disease in body fluids

Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.     

Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer’s disease

The currently available therapies for Alzheimer’s disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies.