Neuroscience
-
LIMK2 is involved in neuronal functions by regulating actin dynamics. Different isoforms of LIMK2 are described in databanks. LIMK2a and LIMK2b are the most characterized. ⋯ Our results also suggest an implication of LIMK2-1 in neurite outgrowth and neurons arborization which appears to be affected by the p. S668P variation. Therefore our results suggest that LIMK2-1 plays a role in the developing brain, and that a rare variation of this isoform is a susceptibility factor in ID.
-
Many human and animal studies have implicated inflammation as a mediator of oxidative stress and a possible contributor to hippocampal atrophy in the pathophysiology of major depressive disorder. We aimed to examine the effect of peripheral, systemic inflammation on oxidative stress and apoptosis in the hippocampi of male and female mice. We hypothesized that (1) lipopolysaccharide (LPS) would induce depressive-like behavior and hippocampal oxidative stress after 1 day in males, and (2) that a single LPS exposure would result in hippocampal apoptosis at 28 days. ⋯ Moreover, males given LPS showed increased apoptosis. Our work will provide insight into the underlying biology in males and females with MDD, and potentially underlying differences between the sexes. Also, our work will hopefully inform optimal clinical treatments that may indeed differ between the sexes.
-
Debilitating and persistent fear memories can rapidly form in humans following exposure to traumatic events. Fear memories can also be generated and studied in animals via Pavlovian fear conditioning. The current study was designed to evaluate basolateral amygdala complex (BLC) involvement following the formation of different fear memories (two contextual fear memories and one adjusted auditory fear memory). ⋯ The adjusted auditory fear conditioning procedure produced memories to a tone, but not to a context. This group, where no contextual fear was present, had a significant reduction in BLC IEG expression. These data suggest background contextual fear memories, created in standard auditory fear conditioning protocols, contribute significantly to increases in amygdala activation.
-
Preclinical evidence suggests that ketamine's rapid and sustained antidepressant actions are due to the induction of synaptogenesis in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP), two brain regions implicated in the pathophysiology of major depression. However, research on the neurobiological effects of ketamine has focused almost exclusively on males. Findings from our group and others indicate that female rodents are more reactive to ketamine's antidepressant effects, since they respond to lower doses in antidepressant-predictive behavioral models. ⋯ Ketamine activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in prefrontocortical synaptoneurosomes, and enhanced spine formation in the male mPFC and HIPP. In females, ketamine induced a sustained increase in hippocampal spine density. Overall, these data exposed a sharp sex difference in the synaptogenic response to ketamine in stress-naïve mice, and further suggest that the mPFC may play a more important role in mediating the antidepressant effects of the drug in males, while the HIPP may be more important for females.
-
Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary cultured NS/PCs and in those of the adult mouse brain. ⋯ Although pathological and functional damages in the hippocampus induced by the neurotoxin trimethyltin were not significantly different between wild-type and Nox4-/- mice, the post-injury reactive proliferation of NS/PCs and neurogenesis in the subgranular zone (SGZ) of the dentate gyrus were significantly impaired in Nox4-/- animals. Restoration from the trimethyltin-induced impairment in recognition and spatial working memory was also significantly attenuated in Nox4-/- mice. Collectively, our findings suggest that Nox4 participates in NS/PC proliferation and neurogenesis in the hippocampus following injury, thereby helping to restore memory function.