Epilepsy & hyperthermia in rats


Many mild preconditioning stress conditions, including physical and metabolic injuries, increase the resistance of neurons to subsequent more severe stresses of the same or different type. This “tolerance phenomenon” lasts one to several weeks, providing a unique opportunity to investigate endogenous neuroprotective mechanisms. The aim of this study was to find a physiological and easily applicable preconditioning stimulus able to confer protection against convulsant-induced neuronal damage and seizures. We found that moderate transient hyperthermic preconditioning markedly reduced kainic-acid-induced neuronal cell loss and attenuated susceptibility to bicuculline-induced seizures. Prevention of cell damage (approximately 50%) was efficient both in vitro in organotypic hippocampal slice cultures and in vivo in adult rats. This protection lasted about 1 week and peaked 3 to 5 days after pretreatment. Unraveling the mechanisms of heat shock preconditioning-induced protection against epilepsy should lead to the development of new therapeutic strategies. (via.)


Stress-related Gene (MKP-1 or MKP1), Depression, and Heat Stress


Duman’s team did whole genome scans on tissue samples from 21 deceased individuals who had been diagnosed with depression and compared gene expression levels to those of 18 individuals who had not been diagnosed with depression. They found that one gene called MKP-1 was increased more than two-fold in the brain tissues of depressed individuals.

This was particularly exciting, say the researchers, because the gene inactivates a molecular pathway crucial to the survival and function of neurons and its impairment has been implicated in depression as well as other disorders. Duman’s team also found that when the MKP-1 gene is knocked out in mice, the mice become resilient to stress. When the gene is activated, mice exhibit symptoms that mimic depression.

The finding that a negative regulator of a key neuronal signaling pathway is increased in depression also identifies MKP-1 as a potential target for a novel class of therapeutic agents, particularly for treatment resistant depression. (via.)

Interesting tidbits from elsewhere: