During hibernation, mammals like the 13-lined ground squirrel cycle between physiological extremes. Most of the hibernation season is spent in bouts of torpor, where body temperature, heart rate, and cerebral blood flow are all very low. However, the ground squirrels periodically enter into interbout arousals (IBAs), where physiological parameters return to non-hibernating levels. During torpor, neurons in many brain regions shrink and become electrically quiescent, but reconnect and regain activity during IBA. Previous work showed evidence of extracellular matrix (ECM) changes occurring in the hypothalamus during hibernation that could be associated with this plasticity. Here, we examined expression of a specialized ECM structure, the perineuronal net (PNN), in the forebrain of ground squirrels in torpor, IBA, and summer (non-hibernating). PNNs are known to restrict plasticity, and could be important for retaining essential connections in the brain during hibernation. We found PNNs in three regions of the hypothalamus: ventrolateral hypothalamus, paraventricular nucleus (PVN), and anterior hypothalamic area. We also found PNNs throughout the cerebral cortex, amygdala, and lateral septum. The total area covered by PNNs within the PVN was significantly higher during IBA compared to non-hibernating and torpor (P < 0.01). Additionally, the amount of PNN coverage area per Nissl-stained neuron in the PVN was significantly higher in hibernation compared to non-hibernating (P < 0.05). No other significant differences were found across seasons. The PVN is involved in food intake and homeostasis, and PNNs found here could be essential for retaining vital life functions during hibernation
- PMID: 31748912
- DOI: 10.1007/s00429-019-01983-w
Mammalian hibernation is a seasonal phenomenon. The hibernation season consists of torpor periods with a reduced body temperature (Tb), interrupted by euthermic arousal periods (interbout arousal, IBA). The physiological changes associated with hibernation are assumed to be under genetic control. However, the molecular mechanisms that govern hibernation-associated gene regulation are still unclear. We found that HSP70 transcription is upregulated in the liver of nonhibernating (summer-active) chipmunks compared with hibernating (winter-torpid) ones. In parallel, HSF1, the major transcription factor for HSP70 expression, is abundant in the liver-cell nuclei of nonhibernating chipmunks, and disappears from the nuclei of hibernating ones. Moreover, during IBA, HSF1 reappears in the nuclei and drives HSP70 transcription. In mouse liver, HSF1 is regulated by the daily Tb rhythm, and acts as a circadian transcription factor. Taken together, chipmunks similarly use the Tb rhythm to regulate gene expression via HSF1 during the torpor-arousal cycle in the hibernation season.
The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 104 pfu (2× LD50) or 106 pfu (170× LD50) and vaccinated the animals with IMVAMUNE® or ACAM2000® either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD50, but not the 170× LD5 challenge. In the 2× LD50 challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE®, but ACAM2000® was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.
- PMID: 32698399
- DOI: 10.3390/vaccines8030396
Context: A disease can be a source of disturbance, causing population declines or extirpations, altering species interactions, and affecting habitat structure. This is particularly relevant for diseases that affect keystone species or ecosystem engineers, leading to potentially cascading effects on ecosystems.
Objective: We investigated the invasion of a non-native disease, plague, to a keystone species, prairie dogs, and documented the resulting extent of fragmentation and habitat loss in western grasslands. Specifically, we assessed how the arrival of plague in the Conata Basin, South Dakota, United States, affected the size, shape, and aggregation of prairie dog colonies, an animal species known to be highly susceptible to plague.
Methods: Colonies in the prairie dog complex were mapped every 1 to 3 years from 1993 to 2015. Plague was first confirmed in 2008 and we compared prairie dog complex and colony characteristics before and after the arrival of plague.
Results: As expected the colony complex and the patches in colonies became smaller and more fragmented after the arrival of plague; the total area of each colony and the mean area per patch within a colony decreased, the number of patches per colony increased, and mean contiguity of each patch decreased, leading to habitat fragmentation.
Conclusion: We demonstrate how an emerging infectious disease can act as a source of disturbance to natural systems and lead to potentially permanent alteration of habitat characteristics. While perhaps not traditionally thought of as a source of ecosystem disturbances, in recent years emerging infectious diseases have shown to be able to have large effects on ecosystems if they affect keystone species.
- PMID: 32701990
- DOI: 10.1371/journal.pone.0235907