The cell cycle–apoptosis connection revisited in the adult brain

Adult neurogenesis is studied in vivo using thymidine analogues such as bromodeoxyuridine (BrdU) to label DNA synthesis during the S phase of the cell cycle. However, BrdU may also label DNA synthesis events not directly related to cell proliferation, such as DNA repair and/or abortive reentry into the cell cycle, which can occur as part of an apoptotic process in postmitotic neurons. In this study, we used three well-characterized models of injury-induced neuronal apoptosis and the combined visualization of cell birth (BrdU labeling) and death (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of BrdU incorporation in the adult mouse brain in vivo. We present evidence that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of BrdU is directly infused into the brain. These findings have important implications for a controversy surrounding adult neurogenesis: the connection between cell cycle reactivation and apoptosis of terminally differentiated neurons

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain

BACKGROUND: In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. RESULTS: Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm(3)) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. CONCLUSIONS: In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes

TrkB signaling is required for postnatal survival of CNS neurons and protects hippocampal and motor neurons from axotomy-induced cell death

Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (¿/¿) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. Furthermore, axotomized hippocampal and motor neurons of trkB (¿/¿) mice have significantly lower survival rates than those of wild-type littermates. These results suggest that neurotrophin signaling through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury- and axotomy-induced cell death

Life, Life Support, and Death Principles, Guidelines, Policies and Procedures for Making Decisions That Respect Life

The following is the third edition of a booklet by the American Life League, Inc. The section on Ordinary/Extraordinary Means has been revised. The sections on Quality of Life, Pain, Paired Organ and Non-vital Organ and Tissue Transplant, and Determination of Death have been added. There are other changes throughout the booklet

The body as unwarranted life support: a new perspective on euthanasia

It is widely accepted in clinical ethics that removing a patient from a ventilator at the patient's request is ethically permissible. This constitutes voluntary passive euthanasia. However, voluntary active euthanasia, such as giving a patient a lethal overdose with the intention of ending that patient's life, is ethically proscribed, as is assisted suicide, such as providing a patient with lethal pills or a lethal infusion. Proponents of voluntary active euthanasia and assisted suicide have argued that the distinction between killing and letting die is flawed and that there is no real difference between actively ending someone's life and "merely" allowing them to die. This paper shows that, although this view is correct, there is even less of a distinction than is commonly acknowledged in the literature. It does so by suggesting a new perspective that more accurately reflects the moral features of end-of-life situations: if a patient is mentally competent and wants to die, his body itself constitutes unwarranted life support unfairly prolonging his or her mental life

Alligator Diet in Relation to Alligator Mortality on Lake Griffin, FL

Alligator mississippiensis (American Alligators) demonstrated low hatchrate success and increased adult mortality on Lake Griffin, FL, between 1998 and 2003. Dying Lake Griffin alligators with symptoms of poor motor coordination were reported to show specific neurological impairment and brain lesions. Similar lesions were documented in salmonines that consumed clupeids with high thiaminase levels. Therefore, we investigated the diet of Lake Griffin alligators and compared it with alligator diets from two lakes that exhibited relatively low levels of unexplained alligator mortality to see if consumption of Dorosoma cepedianum (gizzard shad) could be correlated with patterns of mortality. Shad in both lakes Griffin and Apopka had high levels of thiaminase and Lake Apopka alligators were consuming greater amounts of shad relative to Lake Griffin without showing mortality rates similar to Lake Griffin alligators. Therefore, a relationship between shad consumption alone and alligator mortality is not supported

On Evolution of God-Seeking Mind: An Inquiry Into Why Natural Selection Would Favor Imagination and Distortion of Sensory Experience

The earliest known products of human imagination appear to express a primordial concern and struggle with thoughts of dying and of death and mortality. I argue that the structures and processes of imagination evolved in that struggle, in response to debilitating anxieties and fearful states that would accompany an incipient awareness of mortality. Imagination evolved to find that which would make the nascent apprehension of death more bearable, to engage in a search for alternative perceptions of death: a search that was beyond the capability of the external senses. I argue that imagination evolved as flight and fight adaptations in response to debilitating fears that paralleled an emerging foreknowledge of death. Imagination, and symbolic language to express its perceptions, would eventually lead to religious behavior and the development of cultural supports. Although highly speculative, my argument draws on recent brain studies, and on anthropology, psychology, and linguistics