Consequences of hyperphosphorylated tau on the morphology and excitability of hippocampal neurons in aged tau transgenic mice.

The intracellular accumulation of hyperphosphorylated tau characterizes many neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. A critical role for tau is supported by studies in transgenic mouse models expressing the P301L mutation with accumulation of hyperphosphorylated human tau in hippocampal pyramidal neurons of aged mice. Especially, the somatodendritic mislocalization of hyperphosphorylated tau seems to affect the neuronal network of the hippocampus. To show the consequences of aggregation of hyperphosphorylated tau within hippocampal neurons of aged mice, the CA1 pyramidal cells were analyzed morphologically and electrophysiologically. Here we demonstrate in the P301L pR5 mouse model that hyperphosphorylated tau leads to an increase in stubby spines and filopodia, as well as a decrease in total dendritic length of hippocampal pyramidal neurons due to a decrease in apical dendritic length and nodes. This atrophy is in line with the significant reduction in CA1 long-term potentiation. Furthermore, mutant tau induced a depolarized threshold for action potential initiation and an increased current of inward rectifying potassium channels, which should lead, together with the long-term potentiation decrease, to a decreased excitability of CA1 neurons.

Multivariate Meta-Analysis of Brain-Mass Correlations in Eutherian Mammals.

The general assumption that brain size differences are an adequate proxy for subtler differences in brain organization turned neurobiologists toward the question why some groups of mammals such as primates, elephants, and whales have such remarkably large brains. In this meta-analysis, an extensive sample of eutherian mammals (115 species distributed in 14 orders) provided data about several different biological traits and measures of brain size such as absolute brain mass (AB), relative brain mass (RB; quotient from AB and body mass), and encephalization quotient (EQ). These data were analyzed by established multivariate statistics without taking specific phylogenetic information into account. Species with high AB tend to (1) feed on protein-rich nutrition, (2) have a long lifespan, (3) delayed sexual maturity, and (4) long and rare pregnancies with small litter sizes. Animals with high RB usually have (1) a short life span, (2) reach sexual maturity early, and (3) have short and frequent gestations. Moreover, males of species with high RB also have few potential sexual partners. In contrast, animals with high EQs have (1) a high number of potential sexual partners, (2) delayed sexual maturity, and (3) rare gestations with small litter sizes. Based on these correlations, we conclude that Eutheria with either high AB or high EQ occupy positions at the top of the network of food chains (high trophic levels). Eutheria of low trophic levels can develop a high RB only if they have small body masses.

Genetic structure of the crown-of-thorns seastar in the Pacific Ocean, with focus on Guam.

Population outbreaks of the corallivorous crown-of-thorns seastar (COTS), Acanthaster 'planci' L., are among the most important biological disturbances of tropical coral reefs. Over the past 50 years, several devastating outbreaks have been documented around Guam, an island in the western Pacific Ocean. Previous analyses have shown that in the Pacific Ocean, COTS larval dispersal may be geographically restricted to certain regions. Here, we assess the genetic structure of Pacific COTS populations and compared samples from around Guam with a number of distant localities in the Pacific Ocean, and focused on determining the degree of genetic structure among populations previously considered to be isolated. Using microsatellites, we document substantial genetic structure between 14 localities from different geographical regions in the Pacific Ocean. Populations from the 14 locations sampled were found to be structured in three significantly differentiated groups: (1) all locations immediately around Guam, as well as Kingman Reef and Swains Island; (2) Japan, Philippines, GBR and Vanuatu; and (3) Johnston Atoll, which was significantly different from all other localities. The lack of genetic differentiation between Guam and extremely distant populations from Kingman Reef and Swains Island suggests potential long-distance dispersal of COTS in the Pacific.

Pattern of tau hyperphosphorylation and neurotransmitter markers in the brainstem of senescent tau filament forming transgenic mice.

The early occurrence of brainstem-related symptoms, e.g. gait and balance impairment, apathy and depression in Alzheimer's disease patients suggests brainstem involvement in the initial pathogenesis. To address the question whether tau filament forming mice expressing mutated human tau mirror histopathological changes observed in Alzheimer brainstem, the degree and distribution of neurofibrillary lesions as well as the pattern of cholinergic and monoaminergic neurons were investigated. The expression of the human tau transgene was observed in multiple brainstem nuclei, particularly in the magnocellular reticular formation, vestibular nuclei, cranial nerve motor nuclei, sensory trigeminal nerve nuclei, inferior and superior colliculi, periaqueductal and pontine gray matter, and the red nucleus. Most of the human tau-immunoreactive cell groups also showed tau hyperphosphorylation at the epitopes Thr231/Ser235 and Ser202/Thr205, while abnormal tau phosphorylation at the epitope Ser422 or silver stained structures were almost totally lacking. We found no obvious differences in distribution and density of cholinergic and monoaminergic neurons between tau-transgenic and wild type mice. Although numerous brainstem nuclei in our model expressed human tau protein, the development of neurofibrillary tangles, neuropil threads and ghost tangles was rare and likewise its distribution differed largely from Alzheimer's disease pattern. The number of monoaminergic neurons remained unchanged in the transgenic mice, while monoaminergic nuclei in Alzheimer brainstem showed a distinct neuronal loss. However, the distribution of pretangle-affected neurons in the tau-transgenic mice partly resembled those seen in progressive supranuclear palsy, presenting these animals as a model to examine brainstem pathogenesis of progressive supranuclear palsy.