Intraepidermal Nerve Fiber Density in Postmortem Skin: A Novel Approach.

Objective: To determine the feasibility of examining intraepidermal nerve fiber density (IENFD) in postmortem skin.

Methods: From 12 subjects, 3-mm skin punch biopsies were collected 1-4 days postmortem from the proximal leg and distal leg, with a mean (range) interval from the death of 37 (15-91) hours. Causes of death varied broadly, including hepatocellular carcinoma, chronic lymphocytic leukemia, generalized atherosclerosis, progressive supranuclear palsy, Parkinson disease, emphysema, and obesity.

Low level methylmercury enhances CNTF-evoked STAT3 signaling and glial differentiation in cultured cortical progenitor cells.

Although many previous investigations have studied how mercury compounds cause cell death, sub-cytotoxic levels may affect mechanisms essential for the proper development of the nervous system. The present study investigates whether low doses of methylmercury (MeHg) and mercury chloride (HgCl2) can modulate the activity of JAK/STAT signaling, a pathway that promotes gliogenesis. We report that sub-cytotoxic doses of MeHg enhance ciliary neurotrophic factor (CNTF) evoked STAT3 phosphorylation in human SH-SY5Y neuroblastoma and mouse cortical neural progenitor cells (NPCs).

Neuronal vulnerability in transgenic mice expressing an inducible dominant-negative FGF receptor.

Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) are widely expressed in the mature nervous system and are thought to mediate plasticity and repair. We report the generation of transgenic mice that can be induced to express a dominant-negative FGFR (dnFGFR) in select neuronal populations. We show that a modified Thy1 promoter [Vidal, M.

Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment.

Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice.

Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease.

The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid.

Mouse cerebral prostaglandins, but not oxidative damage, change with age and are responsive to indomethacin treatment.

Epidemiological and clinical trial data indicate that at least some non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of developing Alzheimer's disease (AD). Advancing age is the most robust risk factor for AD. If NSAIDs mitigate the initiation of AD by affecting processes of aging, and if the target of NSAIDs are cyclooxygenases (COX), then COX activity would be hypothesized to increase with advancing age in brain regions affected by AD.