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PubMed2025

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients as an anesthetic and a neuroprotectant used for treating brain injuries. Xe penetrates the blood-brain barrier, which could make it an effective therapeutic. To assess the effect of Xe on microglia and AD pathology, we designed a custom Xe inhalation chamber and treated several mouse models of AD with Xe gas. Xe treatment induced mouse microglia to adopt an intermediate activation state that we have termed pre-neurodegenerative microglia (pre-MGnD). This microglial phenotypic transition was observed in mouse models of acute neurodegeneration and amyloidosis (APP/PS1 and 5xFAD mice) and tauopathy (P301S mice). This microglial state enhanced amyloid plaque compaction and reduced dystrophic neurites in the APP/PS1 and 5xFAD mouse models. Moreover, Xe inhalation reduced brain atrophy and neuroinflammation and improved nest-building behavior in P301S mice. Mechanistically, Xe inhalation induced homeostatic brain microglia toward a pre-MGnD state through IFN-γ signaling that maintained the microglial phagocytic response in APP/PS1 and 5xFAD mice while suppressing the microglial proinflammatory phenotype in P301S mice. These results support the translation of Xe inhalation as an approach for treating AD.

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PubMed2007

Group decision making in nest-site selection among social insects.

The choice of a new nest site is ecologically critical for an insect colony. In swarm-founding social insects, or those that move as colonies from one site to another, this choice is one of the best-available examples of a distributed, nonhierarchical decision-making process in animals. In the few species of ants and bees that have been studied in detail, the main features of this collective decision making are strikingly similar, although some differences occur. Individual scouts discover potential nest sites and integrate multiple properties of these sites into assessments of their quality. The discovered sites then compete for a limited pool of nest-site scouts, and attrition of less-favored sites occurs by several mechanisms. Finally, the mass movement of the colony to the new site is triggered by a quorum-sensing mechanism when sufficient scouts are present at one of the alternatives. Movement itself is coordinated by different mechanisms in different insects.

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PubMed2006

Body temperature changes induced by huddling in breeding male emperor penguins.

Huddling is the key energy-saving mechanism for emperor penguins to endure their 4-mo incubation fast during the Antarctic winter, but the underlying physiological mechanisms of this energy saving have remained elusive. The question is whether their deep body (core) temperature may drop in association with energy sparing, taking into account that successful egg incubation requires a temperature of about 36 degrees C and that ambient temperatures of up to 37.5 degrees C may be reached within tight huddles. Using data loggers implanted into five unrestrained breeding males, we present here the first data on body temperature changes throughout the breeding cycle of emperor penguins, with particular emphasis on huddling bouts. During the pairing period, core temperature decreased progressively from 37.5 +/- 0.4 degrees C to 36.5 +/- 0.3 degrees C, associated with a significant temperature drop of 0.5 +/- 0.3 degrees C during huddling. In case of egg loss, body temperature continued to decrease to 35.5 +/- 0.4 degrees C, with a further 0.9 degrees C decrease during huddling. By contrast, a constant core temperature of 36.9 +/- 0.2 degrees C was maintained during successful incubation, even during huddling, suggesting a trade-off between the demands for successful egg incubation and energy saving. However, such a limited drop in body temperature cannot explain the observed energy savings of breeding emperor penguins. Furthermore, we never observed any signs of hyperthermia in huddling birds that were exposed to ambient temperatures as high as above 35 degrees C. We suggest that the energy savings of huddling birds is due to a metabolic depression, the extent of which depends on a reduction of body surface areas exposed to cold.

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PubMed2000

Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator.

Arctic ground squirrels (Spermophilus parryii) overwinter in hibernaculum conditions that are substantially below freezing. During torpor, captive arctic ground squirrels displayed ambient temperature (T(a))-dependent patterns of core body temperature (T(b)), metabolic rate (TMR), and metabolic fuel use, as determined by respiratory quotient (RQ). At T(a) 0 to -16 degrees C, T(b) remained relatively constant, and TMR rose proportionally with the expanding gradient between T(b) and T(a), increasing >15-fold from a minimum of 0.0115 +/- 0.0012 ml O(2). g(-1). h(-1). At T(a) 0-20 degrees C, T(b) increased with T(a); however, TMR did not change significantly from T(b) 0 to 12 degrees C, indicating temperature-independent inhibition of metabolic rate. The overall change in TMR from T(b) 4 to 20 degrees equates to a Q(10) of 2.4, but within this range of T(b), Q(10) changed from 1.0 to 14.1. During steady-state torpor at T(a) 4 and 8 degrees C, RQ averaged 0.70 +/- 0.013, indicating exclusive lipid catabolism. At T(a) -16 and 20 degrees C, RQ increased significantly to >0.85, consistent with recruitment of nonlipid fuels. RQ was negatively correlated with maximum torpor bout length. For T(a) values <0 degrees C, this relationship supports the hypothesis that availability of nonlipid metabolic fuels limits torpor duration in hibernating mammals; for T(a) values >0 degrees C, hypotheses linked to body temperature are supported. Because anterior body temperatures differ from core, overall, the duration torpor can be extended in hibernating mammals may be dependent on brain temperature.

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PubMed2000

Reward linked to increased natural killer cell activity in rats.

In rats splenic natural killer (NK) cell activity was found to be significantly higher following chronic uncontrollable electrical stimulation of the lateral hypothalamus in fully conscious rats, compared to sham-operated rats. In a pre-test study, all rats had demonstrated that the electrode site had self-stimulating properties, which supports the possibility that the experience of reward may be implicated in NK cell activity augmentation.

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PubMed2005

Evolution of bower complexity and cerebellum size in bowerbirds.

To entice females to mate, male bowerbirds build elaborate displays (bowers). Among species, bowers range in complexity from simple arenas decorated with leaves to complex twig or grass structures decorated with myriad colored objects. To investigate the neural underpinnings of bower building, we examined the contribution of variation in volume estimates of whole brain (WB), telencephalon minus hippocampus (TH), hippocampus (Hp) and cerebellum (Cb) to explain differences in complexity of bowers among 5 species. Using independent contrasts, we found a significant relationship between bower complexity and Cb size. We did not find support for correlated evolution between bower complexity and WB, TH, or Hp volume. These results suggest that skills supported by the cerebellum (e.g., procedural learning, motor planning) contribute to explaining the variation in bower complexity across species. Given that male mating success is in part determined by female choice for bower design, our data are consistent with the hypothesis that sexual selection has driven enlargement of the cerebellum in bowerbirds.

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PubMed1995

A Golgi and horseradish peroxidase study of the sonic motor nucleus of the oyster toadfish.

The sonic motor nucleus (SMN) of the oyster toadfish Opsanus tau, a single midline structure in the occipital spinal cord and caudal medulla, contains large electrically-coupled motoneurons. Although interpretation is complicated by multiyear growth in soma size, neurons in males may be either large (L) or small (S), whereas females have exclusively S neurons. Golgi stains have allowed separation of five neuron variants (rostral, dorsal, stellate, ventral and caudal) which differ in location, soma shape and size, and direction and pattern of dendritic branching. All variants are present in L and S males and in females, and retrograde transport of horseradish peroxidase indicates that all variants are motoneurons. The SMN is organized into three horizontal layers with rostral and dorsal neurons forming a rostrocaudally arrayed network across the dorsal-dorsolateral surface. Stellate cells are found in the middle layer, and ventral cells with laterally directed dendrites that exit the SMN line the inferior surface. Caudal neurons with caudally directed exiting dendrites are arranged in parallel rows in the caudal fifth of the SMN. We suggest that variant differences in dendritic orientation relate to different patterns of innervation by multiple afferents to the SMN and function to maximize contacts between neurons as a means of facilitating synchronization within the nucleus. Sexual dimorphism has been demonstrated to a minor degree: all variants have larger somas in L fish than S fish, but no difference has been found in primary dendrite diameter. Larger somas would potentially support the greater amount of sound production by nesting males who produce a mating boatwhistle call. Equivalent dendrite diameter in females, who are just as likely as males to grunt, an agonistic call, suggests that female Opsanus have a well developed sonic circuitry compared to Porichthys, another toadfish in which females are typically silent.

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