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D G Flood

Publications and source records attributed to D G Flood.

44 records · Page 3Linked to original sources
PubMedDate not supplied

Net dendritic stability of layer II pyramidal neurons in F344 rat entorhinal cortex from 12 to 37 months.

Dendritic extent of Golgi-Cox stained layer II entorhinal cortex pyramidal neurons was quantified in five groups of male F344 rats aged 12, 20, 27, 30 and 37 months. Over the age range studied, neither the apical nor the basal dendritic trees showed any statistically significant change in total dendritic length, numbers of segments or average segment length. This finding of average stability of the dendritic tree does not imply absence of remodelling of connections, but does require that if remodeling does occur, retraction and proliferation of dendrites must, on average, be equal. We hypothesized that in groups of animals with similar genetic and environmental histories neighbor neuron death provides the major stimulus for dendritic proliferation. Since we found dendritic stability in the cells reported here, we would predict that there should be no age-related loss of layer II pyramidal neurons in the entorhinal cortex of the normally aging F344 male rat between 12 and 37 months. This hypothesis may be tested by counting neurons within this region.

Aging↗
PubMedDate not supplied

Profiling of endogenous brain peptides and small proteins: methodology, computer-assisted analysis, and application to aging and lesion models.

Significant advances in the technology for the isolation of peptides and small proteins have permitted their identification as biologic markers and enhanced the study of the posttranslational life of proteins. The protocol described here examined large numbers of tissue-derived peptides and small proteins, extracted in low pH and boiled so that proteolysis was interrupted. These were then fractionated batchwise using size exclusion and ion-exchange chromatography. Profiles of species in the peptide pools were then generated on reverse-phase high-performance liquid chromatography (HPLC). The HPLC profiles were evaluated with chromatographic analysis software to identify and quantify peptide peaks and with data compilation programs to sort this information into spreadsheets for comparison of profiles among groups. Using rodent brain, the effects of postmortem delay or age were examined. Postmortem delay produced limited alterations to the profiles, but the effect of age was more pronounced. Many changes were apparent until 12 months, after which the profiles became more constant. Additional peptide profiling of the hippocampus demonstrated changes in peptide content as a function of perforant pathway ablation. The major strengths of HPLC-mediated peptide profiling are that it lends itself to automation and can be used to detect changes in peptides and small proteins among experimental groups or subjects without any prior assumptions concerning which ones might be altered.

Aged↗
PubMedDate not supplied

Dendritic regression dissociated from neuronal death but associated with partial deafferentation in aging rat supraoptic nucleus.

As neurons are lost in normal aging, the dendrites of surviving neighbor neurons may proliferate, regress, or remain unchanged. In the case of age-related dendritic regression, it has been difficult to distinguish whether the regression precedes neuronal death or whether it is a consequence of loss of afferent supply. The rat supraoptic nucleus (SON) represents a model system in which there is no age-related loss of neurons, but in which there is an age-related loss of afferents. The magnocellular neurosecretory neurons of the SON, that produce vasopressin and oxytocin for release in the posterior pituitary, were studied in male Fischer 344 rats at 3, 12, 20, 27, 30, and 32 months of age. Counts in Nissl-stained sections showed no neuronal loss with age, and confirmed similar findings in other strains of rat and in mouse and human. Nucleolar size increased between 3 and 12 months of age, due, in part, to nucleolar fusion, and was unchanged between 12 and 32 months of age, indicating maintenance of general cellular function in old age. Dendritic extent quantified in Golgi-stained tissue increased between 3 and 12 months of age, was stable between 12 and 20 months, and decreased between 20 and 27 months. We interpret the increase between 3 and 12 months as a late maturational change. Dendritic regression between 20 and 27 months was probably the result of deafferentation due to the preceding age-related loss of the noradrenergic input to the SON from the ventral medulla.

Aging↗
PubMedDate not supplied

Neuron numbers and sizes in aging brain: comparisons of human, monkey, and rodent data.

One of the several sources of interest in aging animal brains is their potential as models of the aging human brain. In this review we examine whether neuron numbers and sizes change similarly in aging human, monkey and rodent brain regions which data are available from more than one species. The number of brain regions studied in more than one species is surprisingly limited. Some regions show correspondence in age-related changes between humans and selected animal models (primary visual cortex, CA1 of hippocampus). For the majority of regions the data are conflicting, even within one species (e.g., somatosensory cortex, frontal cortex, cerebellum, cholinergic forebrain areas, locus coeruleus). Although some of the conflicting data may be attributed to procedural differences, particularly when data are expressed as density changes, much must be attributed to real species and/or strain differences in rodents. We conclude that neuron numbers and sizes may show similar age-related changes in human and animal brains only for sharply defined brain regions, animal species and/or strains, and age ranges.

Aging↗
PubMedDate not supplied

Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase.

Age-related hearing loss in humans and many strains of mice is associated with a base-to-apex gradient of cochlear hair cell loss. To determine if copper/zinc superoxide dismutase (Cu/Zn SOD) deficiency influences age-related cochlear pathology, we compared hair cell losses in cochleas obtained from 2-, 7-, and 17- to 19-month-old wild type (WT) mice with normal levels of Cu/Zn SOD and mutant knockout (KO) mice with a targeted deletion of Sod1, the gene that codes for Cu/Zn SOD. WT and KO mice exhibited similar patterns of hair cell loss with age, i.e., a baso-apical progression of hair cell loss, with greater loss of outer hair cells than inner hair cells. Within each age group, the magnitude of loss was much greater in KO mice compared to WT mice. The results indicate that Cu/Zn SOD deficiency potentiates cochlear hair cell degeneration, presumably through metabolic pathways involving the superoxide radical.

Aging↗
PubMedDate not supplied

Targeted deletion of the cytosolic Cu/Zn-superoxide dismutase gene (Sod1) increases susceptibility to noise-induced hearing loss.

Reactive oxygen species (ROS) such as superoxide, peroxide and hydroxyl radicals are generated during normal cellular metabolism and are increased in acute injury and in many chronic disease states. When their production is inadequately regulated, ROS accumulate and irreversibly damage cell components, causing impaired cellular function and death. Antioxidant enzymes such as superoxide dismutase (SOD) play a vital role in minimizing ROS levels and ROS-mediated damage. The cytosolic form of Cu/Zn-SOD appears specialized to remove superoxide produced as a result of injury. 'Knockout' mice with targeted deletion of Sod1, the gene that codes for Cu/Zn-SOD, develop normally but show enhanced susceptibility to central nervous system injury. Since loud noise is injurious to the cochlea and is associated with elevated cochlear ROS, we hypothesized that Sod1 knockout mice would be more susceptible to noise-induced permanent threshold shifts (PTS) than wild-type and heterozygous control mice. Fifty-nine mice (15 knockout, 29 heterozygous and 15 wild type for Sod1) were exposed to broad-band noise (4.0-45.0 kHz) at 110 dB SPL for 1 h. Hearing sensitivity was evaluated at 5, 10, 20 and 40 kHz using auditory brainstem responses before exposure and 1, 14 and 28 days afterward. Cu/Zn-SOD deficiency led to minor (0-7 dB) threshold elevations prior to noise exposure, and about 10 dB of additional noise-induced PTS at all test frequencies, compared to controls. The distribution of thresholds at 10 and 20 kHz at 28 days following exposure contained three modes, each showing an effect of Cu/Zn-SOD deficiency. Thus another factor, possibly an additional unlinked gene, may account for the majority of the observed PTS. Our results indicate that genes involved in ROS regulation can impact the vulnerability of the cochlea to noise-induced hearing loss.

Alleles↗