Motor impairment and neuronal damage following hypothermia in tropical amphibians

Abstract

Although the induction of mild to moderate cerebral hypothermia in mammals can have neuroprotective activity, some deleterious effects have been described when inducing deep hypothermia during cooling of the brain. In the spinal cord, rapid deep cooling can induce seizure activity accompanied by release of the excitatory neurotransmitters, glutamate and aspartate. We used cold-sensitive tropical amphibians as a model to determine (a) the critical temperature inside the central nervous system necessary to induce seizures during rapid cooling; (b) the survival rate during slow deep cooling of the whole animal; and (c) whether deep cooling can cause neuronal cell damage. Seizures induced by deep rapid (<or=3 min) cooling of the spinal cord began when a critical temperature of 10.4 degrees C was reached. During slow (>or=30 min) deep cooling of the whole animal (12 h at 2-3 degrees C), around 70% of animals died. Spinal reflexes were enhanced when temperatures within the spinal cord reached between 9.0 degrees C and 11.6 degrees C. A fivefold increase in blood glucose level was observed during slow deep cooling. Recovery after slow deep cooling was accompanied by motor impairment and the main histological findings were condensation of the cytoplasm and nuclear pyknosis. Severe neuronal cell damage was characterized by swelling, vacuolated cytoplasm with distended neuronal bodies. These results indicate that deep cooling can easily induce neuronal cell damage in the central nervous system of cold-sensitive animals. They also warn us to the potential sequels associated with the use of deep brain cooling as a neuroprotective strategy.

Admixture has obscured signals of historical hard sweeps in humans

“…Four of the metabolic pathways shared across multiple ancient populations ( Figure 5) are collagen specific -a metabolic process that has been shown to be a frequent target of selection in mammals living in circumpolar regions (Yudin et al, 2017). In addition, six of the eight sweeps with either a single gene or a single biological process are Ancestral West Eurasian (>35kya), and are either involved in lipid metabolism (two sweeps) or with nervous tissue maintenance (four sweeps) (Material and Methods), both of which have been associated with adaptation to cold environments (Brandefelt et al, 2011;Daló et al, 2007;Nedergaard and Cannon, 2018). A potential association with cold adaptation is interesting as this has been identified as a likely important factor as Anatomically Modern Humans (AMH) first moved into Eurasian environments (Silvert et al, 2019) -which were around 5°C cooler than those of their northern African origins at 55-50kya (Brandefelt et al, 2011) (Material and Methods).…”

“…Previous studies have also shown that cold environments can lead to neuropathy through a number of different mechanisms, some of which involve genes identified in our sweeps. For example, in vivo experiments in amphibians and mammals show that hypothermic conditions trigger excessive electrochemical signaling in spinal cord neurons, leading to imbalances in neuronal ionic composition and cell death (Daló et al, 2007;Li et al, 2015). NFASC and DOK5 may have preventative roles in this context:…”