A study was made at electron microscope level of changes in the three-dimensional (3-D) morphology of dendritic spines and postsynaptic densities (PSDs) in CA1 of the hippocampus in ground squirrels, taken either at low temperature during hibernation (brain temperature 2-4 degrees C), or after warming and recovery to the normothermic state (34 degrees C). In addition, the morphology of PSDs and spines was measured in a non-hibernating mammal, rat, subjected to cooling at 2 degrees C at which time core rectal temperature was 15 degrees C, and then after warming to normothermic conditions. Significant differences were found in the proportion of thin and stubby spines, and shaft synapses in CA1 for rats and ground squirrels for normothermia compared with cooling or hibernation. Hypothermia induced a decrease in the proportion of thin spines, and an increase in stubby and shaft spines, but no change in the proportion of mushroom spines. The changes in redistribution of these three categories of spines in ground squirrel are more prominent than in rat. There were no significant differences in synapse density determined for ground squirrels or rats at normal compared with low temperature. Measurement of spine and PSD volume (for mushroom and thin spines) also showed no significant differences between the two functional states in either rats or ground squirrels, nor were there any differences in distances between neighboring synapses. Spinules on dendritic shafts were notable qualitatively during hibernation, but absent in normothermia. These data show that hypothermia results in morphological changes which are essentially similar in both a hibernating and a non-hibernating animal.
"These changes have been characterized in other species of ground squirrels and include: a large decrease in pyramidal cell soma size   , decreases in dendritic branching and spine density of CA1 and CA3 cells   , fewer mossy fiber terminals   and up to a 65% loss of synapses  . Upon arousal from hibernation, there is a rapid increase in cell soma size, dendritic branching and spine density within several hours     and this appears to parallel a recovery of function based on behavioral tests . However, none of these studies examined sex as a variable. "
[Show abstract][Hide abstract] ABSTRACT: Studies across and within species suggest that hippocampus size is sexually dimorphic in polygamous species, but not in monogamous species. Although hippocampal volume varies with sex, season and mating system, few studies have simultaneously tested for sex and seasonal differences. Here, we test for sex and seasonal differences in the hippocampal volume of wild Richardson's ground squirrels (Urocitellus richardsonii), a polygamous species that lives in matrilineal, kin-based social groups and has profound sex differences in behavior. Based on the behavior and ecology of this species, we predicted that males would have a significantly larger hippocampus than females and that the hippocampus would be largest in males during the breeding season. Analyses of both absolute and relative volumes of the hippocampus yielded a significant difference between the sexes and seasons as well as an interaction between the two such that non-breeding males have significantly larger hippocampal volumes than breeding males or females from either season. Dentate gyrus, CA1 and CA3 subfield volumes were generally larger in the non-breeding season and in males, but no significant interaction effects were detected. This sex and seasonal variation in hippocampal volume is likely the result of their social organization and male-only food caching behavior during the non-breeding season. The demonstration of a sex and seasonal variation in hippocampal volume suggests that Richardson's ground squirrel may be a useful model for understanding hippocampal plasticity within a natural context.
Behavioural brain research 09/2012; 236(1):131-8. DOI:10.1016/j.bbr.2012.08.044 · 3.03 Impact Factor
"In neurons, several key aspects of synaptic transmission, including the distribution of postsynaptic neurotransmitter receptors, postsynaptic ion fluxes, and the spread of presynaptically released neurotransmitters, are strongly influenced by the shapes of dendritic spines. Hypothermia is known to induce changes in the shape of dendritic spines . Dendritic spines are highly sensitive to hypothermia and rapidly lose actin-based motility followed by the reversible loss of the entire spine structure. "
[Show abstract][Hide abstract] ABSTRACT: Induced therapeutic hypothermia is the one of the most effective tools against brain injury and inflammation. Even though its beneficial effects are well known, there are a lot of pitfalls to overcome, since the potential adverse effects of systemic hypothermia are still troublesome. Without the knowledge of the precise mechanisms of hypothermia, it will be difficult to tackle the application of hypothermia in clinical fields. Better understanding of the characteristics and modes of hypothermic actions may further extend the usage of hypothermia by developing novel drugs based on the hypothermic mechanisms or by combining hypothermia with other therapeutic modalities such as neuroprotective drugs. In this review, we describe the potential therapeutic targets for the development of new drugs, with a focus on signal pathways, gene expression, and structural changes of cells. Theapeutic hypothermia has been shown to attenuate neuroinflammation by reducing the production of reactive oxygen species and proinflammatory mediators in the central nervous system. Along with the mechanism-based drug targets, applications of therapeutic hypothermia in combination with drug treatment will also be discussed in this review.
DNA research: an international journal for rapid publication of reports on genes and genomes 03/2012; 10(1):80-7. DOI:10.2174/157015912799362751 · 3.05 Impact Factor
"Most hibernators periodically interrupt the state of hibernation (torpor) by euthermic episodes or arousal, a process responsible for up to 90% of the energy consumed during hibernation. Previously, using Golgi and electron microscope studies in hippocampal tissue of hibernating ground squirrels we have shown marked structural alterations in the components of neural circuitry, with the reversible retraction of dendritic spines and synapses in CA1 and CA3  . "
[Show abstract][Hide abstract] ABSTRACT: Neurogenesis occurs in the adult mammalian hippocampus, a region of the brain important for learning and memory. Hibernation in Siberian ground squirrels provides a natural model to study mitosis as the rapid fall in body temperature in 24 h (from 35-36°C to +4-6°C) permits accumulation of mitotic cells at different stages of the cell cycle. Histological methods used to study adult neurogenesis are limited largely to fixed tissue, and the mitotic state elucidated depends on the specific phase of mitosis at the time of day. However, using an immunohistochemical study of doublecortin (DCX) and BrdU-labelled neurons, we demonstrate that the dentate gyrus of the ground squirrel hippocampus contains a population of immature cells which appear to possess mitotic activity. Our data suggest that doublecortin-labelled immature cells exist in a mitotic state and may represent a renewable pool for generation of new neurons within the dentate gyrus.
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