Actin' up (and down)

The C?te D'Azure provided a stunning backdrop for a recent conference* on the role of microfilament function and regulation in cell polarity. Although sadly missing several North American participants in the wake of events in Washington and New York, the largely European audience was nevertheless treated to fascinating insights into the many roles of actin polymerization and other processes involved in the establishment and maintenance of cell polarity. (*Joint CNRS/Jacques Monod/EMBO Conference on 'The Role of Microfilament Function and Regulation in Cell Polarity'; Presqu'ile de Giens, France 15-19 Sept 2001. Organized by Daniel Louvard and Tony Bretscher.)     

Stem cell review series: role of neurogenesis in age-related memory disorders

Neuroplasticity is characterized by growth and branching of dendrites, remodeling of synaptic contacts, and neurogenesis, thus allowing the brain to adapt to changes over time. It is maintained in adulthood but strongly repressed during aging. An age-related decline in neurogenesis is particularly pronounced in the two adult neurogenic areas, the subventricular zone and the dentate gyrus. This age-related decline seems to be attributable mainly to limited proliferation, associated with an age-dependent increase in quiescence and/or a lengthening of the cell cycle, and is closely dependent on environmental changes. Indeed, when triggered by appropriate signals, neurogenesis can be reactivated in senescent brains, thus confirming the idea that the age-related decrease in new neuron production is not an irreversible, cell-intrinsic process. The coevolution of neurogenesis and age-related memory deficits – especially regarding spatial memory – during senescence supports the idea that new neurons in the adult brain participate in memory processing, and that a reduction in the ability to generate new neurons contributes to the appearance of memory deficits with advanced age. Furthermore, the age-related changes in hippocampal plasticity and function are under environmental influences that can favor successful or pathological aging. A better understanding of the mechanisms that regulate neurogenesis is necessary to develop new therapeutic tools to cure or prevent the development of memory disorders that may appear during the course of aging in some individuals.     

Knocked down and out: PACAP in development, reproduction and feeding

One approach to understanding the role of PACAP in vivo is to knockdown the translation of PACAP mRNA to protein or to knock out the PACAP gene by targeted disruption. In this paper, we review the effect of PACAP knockdown with morpholinos on early brain development in zebrafish. Also reviewed is the role of PACAP at several stages of reproduction as assessed in mice with a disrupted PACAP gene. New data are presented to analyze PACAP's action in energy homeostasis (body mass, food intake, endocrine parameters) using female PACAP-null mice. The evidence suggests PACAP is important for brain development in zebrafish and is required for normal reproduction, but not for body mass or food intake in mice maintained near thermoneutrality.     

Hippocampal neurogenesis and neuroinflammation after cranial irradiation with (56)Fe particles

Exposure to heavy-ion radiation is considered a potential health risk in long-term space travel. In the central nervous system (CNS), loss of critical cellular components may lead to performance decrements that could ultimately compromise mission goals and long-term quality of life. Hippocampal-dependent cognitive impairments occur after exposure to ionizing radiation, and while the pathogenesis of this effect is not yet clear, it may involve the production of newly born neurons (neurogenesis) in the hippocampal dentate gyrus. We irradiated mice with 0.5-4 Gy of (56)Fe ions and 2 months later quantified neurogenesis and numbers of activated microglia as a measure of neuroinflammation in the dentate gyrus. Results showed that there were few changes after 0.5 Gy, but that there was a dose-related decrease in hippocampal neurogenesis and a dose-related increase in numbers of newly born activated microglia from 0.5-4.0 Gy. While those findings were similar to what was reported after X irradiation, there were also some differences, particularly in the response of newly born glia. Overall, this study showed that hippocampal neurogenesis was sensitive to relatively low doses of (56)Fe particles, and that those effects were associated with neuroinflammation. Whether these changes will result in functional impairments or if/how they can be managed are topics for further investigation.     

Methyl-DNA immunoprecipitation (MeDIP): hunting down the DNA methylome

One of the most challenging projects in the field of epigenetics is the generation of detailed functional maps of DNA methylation in different cell and tissue types in normal and disease-associated conditions. This information will help us not only understand the role of DNA methylation but also identify targets for therapeutic treatment. The completion of the various epigenome projects depends on the design of novel strategies to survey and generate detailed cartograms of the DNA methylome. Methyl-DNA immunoprecipitation (MeDIP) assays, in combination with hybridization on high-resolution microarrays or high-throughput sequencing (HTS) techniques, are excellent methods for identifying methylated CpG-rich sequences. We provide a critical overview of different genome-wide techniques for DNA methylation analysis and propose that MeDIP assays may constitute a key method for elucidating the hypermethylome of cancer cells.     

Psychiatric illness in inpatients with neurological disorders: patients' views on discussion of emotional problems with neurologists.

The prevalence of psychiatric morbidity in inpatients with neurological disorders and the extent to which it is detected by neurologists were measured by using a two stage model of psychiatric assessment and from information recorded in the patients'' medical notes. The prevalence of psychiatric morbidity was estimated as 39%, of which 72% was unrecognised by the neurologists. Only a minority of patients with an uncertain physical diagnosis had a psychiatric illness, showing the error in assuming that a patient''s physical symptoms arise from a psychological disturbance if an organic aetiology cannot be determined. When the patients were interviewed on their discharge from hospital they were divided on whether they had wished to discuss their mood with neurologists while they were in hospital. The reasons that they gave suggested that interactions between patients and doctors and the lack of ward facilities for private consultations with doctors are important determinants of hidden psychiatric morbidity in medical inpatients.     

Psychiatric Aspects of Artificial Insemination (Donor)

Artificial insemination (donor) [A.I.D.] in humans is a medical procedure that has been carried out for roughly 50 years. Its legal status has not yet been established; its moral implications are still hotly contested, and its psychological and psychiatric implications are only now coming under scientific scrutiny.The use of this procedure in couples who are psychologically unsuited for it can have unfortunate consequences. The obstetrician should seek the assistance of a dynamically oriented psychiatrist in screening couples who ask for artificial insemination (donor).Parenthood, in line with psychoanalytic ego psychology, is seen as a phase of ego development. The potential for mothering and fathering children is a later stage in growth than the capacity to conceive and sire them. It is the psychiatrist''s role to assess the couple''s motivation for A.I.D. in the light of the extent to which they have achieved this degree of ego development.