Juvenile stress causes reduced locomotor behavior and dendritic spine density in the prefrontal cortex and basolateral amygdala in Sprague-Dawley rats.

Little has been investigated about the effects of stress on synaptic communication at prepubertal age, a stage considered as juvenile. This period of development is related to socialization through play. Our group has studied the changes of neuronal morphology in limbic structures caused by stress at prenatal and at early postnatal ages (before weaning) in the rat. In the present study, we assessed the effect of restraint stress at juvenile ages. Male Sprague-Dawley rats from postnatal day (PD) 21 to PD35 were restrained (from movement) for 2 hrs. Locomotor activity in a novel environment was evaluated at three different ages, prepubertal PD38, pubertal PD50, and postpubertal PD68. Using the Golgi-Cox procedure, the dendritic morphology was evaluated in the pyramidal neurons of the prefrontal cortex (PFC), hippocampus, and basolateral amygdala (BLA). Juvenile stress caused a reduced locomotor activity at PD38 and PD68 together with reduction in dendritic spines after puberty in the PFC and at all the studied ages in the BLA. In addition, dendritic length was also reduced in the PFC at PD38 and PD68 and CA1 of the ventral hippocampus at PD50 and PD68. Our results suggest that stress in the juvenile stage can cause changes at the level of behavior and synaptic communication with an effect that remains until adulthood.

HRS-4642: The next piece of the puzzle to keep KRAS in check.

KRASG12D is the most frequent KRAS mutation in human cancer. In this issue, Zhou et al. describe a novel KRASG12D inhibitor, HRS-4642, that shows potent and selective anti-tumor activity across various models and synergizes with proteasome inhibitors. Responses have also been observed in patients during an ongoing phase 1 trial.