Changes in neocortical and hippocampal microglial cells during hibernation

Abstract

Mammalian hibernation proceeds alongside a wide range of complex brain adaptive changes that appear to protect the brain from extreme hypoxia and hypothermia. Using immunofluorescence, confocal microscopy, quantitative analysis methods and intracellular injections, we have characterized microglia morphological changes that occur in the neocortex and hippocampus of the Syrian hamster during hibernation. In euthermic hamsters, microglial cells showed the typical ramified/resting morphology with multiple long, thin and highly-branched processes homogeneously immunostained for Iba-1. However, during torpor, microglial cell process numbers increase significantly accompanied by a shortening of the Iba-1 immunoreactive processes, which show a fragmented appearance. Adaptative changes of microglial cells during torpor coursed with no expression of microglial cell activation markers. We discuss the possibility that these morphological changes may contribute to neuronal damage prevention during hibernation.

Phosphorylation and Dephosphorylation of Tau Protein During Synthetic Torpor

“…Considering the limitation of our analysis, carried out in only one subject per condition, no relevant modifications in cell morphology, which are considered to be a sign of microglia activation (Stence et al, 2001; Morrison and Filosa, 2013), were observed throughout the experimental protocol in any structure analyzed, as shown in Supplementary Figure S1 for CA3. Although some changes in hippocampal microglia morphology were observed in hibernating hamsters (Cogut et al, 2018; León-Espinosa et al, 2018), a normalization to the euthermic control values occurred at the eighth hour from the end of the torpor bout (Cogut et al, 2018).…”

Multiple Morphometric Assessment of Microglial Cells in Deafferented Spinal Trigeminal Nucleus

“…to guarantee complete penetration of the immunolabeling but which cannot ensure that the whole set of processes is included in the section. From intracellularly filled and presumably fully labeled MG in very thick (up to 200 µm) slices, the mean linear span of relatively isotropic cells reaches at least 60-90 µm in different brain regions (Hayashi et al, 2013;De Biase et al, 2017;Leon-Espinosa et al, 2018).…”

“…On the other hand, changes in number, size, and shape are stereotypical features of MG "activation" in general, and particularly in all cases of experimental models of nerve injury (Beggs and Salter, 2007;Calvo and Bennett, 2012). Unsurprisingly, morphometry continues to contribute key parameters to assess the dynamics of MG and gain insights into its function (Tremblay et al, 2010;Kettenmann et al, 2011;Beynon and Walker, 2012;Morrison and Filosa, 2013;Parada et al, 2015;Ohgomori et al, 2016;Leon-Espinosa et al, 2018). However, an optimal morphometric approach that yields unbiased results with functional significance and growing efficiency is yet to be found.…”

The Golgi Apparatus of Neocortical Glial Cells During Hibernation in the Syrian Hamster

“…Previous studies have demonstrated that the state of torpor is accompanied by a variety of complex adaptive and reversible brain changes that appear to protect the brain from hypoxia and low Tb. These brain changes during torpor include a decrease in adult neurogenesis; alterations in dendritic trees including dendritic spine retraction; a decrease in synaptic connections; the fragmentation and reduction of the neuronal GA; and an increase in length of the axon initial segment (Popov and Bocharova, 1992; Popov et al, 1992, 2007, 2011; Von Der Ohe et al, 2006, 2007; Antón-Fernández et al, 2015; Bullmann et al, 2016; Leon-Espinosa et al, 2016, 2018).…”

“…In addition to these neuronal changes, it has been reported that there is a reduction in the microglial reaction produced by the insertion of microdialysis probes (Zhou et al, 2001) in hibernating arctic ground squirrels. This could be related to the morphological and neurochemical changes that take place in microglial cells during torpor, which show a dystrophic phenotype including an increase in the number and the shortening of Iba-1-ir processes, which show an overall fragmented appearance with thinning at some segments and swellings at others (Leon-Espinosa et al, 2018). Knowledge of the structural organization of the GA of glial cells of the neocortex is fragmentary and limited to pioneering studies with silver staining (Del Rio Hortega, 1919), electron microscopy (Peters et al, 1991), and in vitro observations (Lavi et al, 1994).…”