Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina?

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models

Review: Tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain?

Tau protein’s versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer’s disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve

Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD

Pharmacodynamics of growth hormone abuse biomarkers and the influence of gender and testosterone : a randomized double-blind placebo-controlled study in young recreational athletes

Context: IGF axis proteins and collagen peptides are promising markers of GH abuse. Objective: Our objective was to investigate whether responses of serum IGF axis and collagen markers to GH differ between men and women, and are influenced by testosterone (T). Design: This was a randomized, double-blind, placebo-controlled study of 8-wk treatment followed by 6-wk washout. Setting: The study was performed at a clinical research facility. Participants: A total of 96 recreationally trained healthy athletes (63 men, 33 women), aged 18-40 yr, were studied. Intervention: All subjects received GH (2 mg/d sc) or placebo for 8 wk; men also received T (250 mg/wk im) or placebo for 5 wk. Main Outcome Measures: Serum IGF axis proteins (IGF-I, IGF binding protein-3, and acid labile subunit) and collagen peptides (N-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type III procollagen) were measured. Results: GH induced significant increases in IGF axis and collagen markers that were greater in men than women (P < 0.001). Of the IGF axis markers, IGF-I showed the greatest increase. The relative incremental responses of the collagen markers in generalweregreater than the IGF markers, especially for PIIINP. The collagen markers increased and decreased more slowly with most remaining elevated (P < 0.01) after 6 wk, in comparison to IGF markers, which returned to baseline within 1 wk. Addition of T to GH amplified the response of PIIINP by more than 1.5-fold but did not affect any other marker. T alone did not affect IGF axis markers but modestly increased collagen markers. Conclusions: These markers of GH abuse are less responsive in women. The increases in collagen markers have a different time course to the IGF markers and extend the window of detection in both sexes. The response of PIIINP is increased by coadministration of T