Behavioural and EEG effects of chronic rapamycin treatment in a mouse model of Tuberous Sclerosis Complex

Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats

“…Hyperactive PI3K/Akt/mTOR signaling has been well characterized in epilepsy-associated memory deficits (Ehninger et al, 2008; Brewster et al, 2013; Cambiaghi et al, 2013; Trinh and Klann, 2013; Lugo et al, 2014). Recently, Zhang and Wong (2012) reported that a single generalized seizure was sufficient to cause dysregulated signaling of PI3K/Akt/mTOR pathway.…”

Dendritic spine dysgenesis in autism related disorders

“…Though there are many factors and pathways involved in the pruning of dendritic spines and their excitatory synapses, these correlations suggest that mTOR is a potential site of therapeutic intervention for autism-related disorders. In support of this notion, studies in both FXS and TS show alleviation of both synaptic and behavioral phenotypes after treatment of the mTOR inhibitor rapamycin [227, 228]. It is tempting to speculate that similar treatments will be effective to alleviate synaptopathologies and autistic behaviors in other ARDs.…”

Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release

“…Several studies demonstrated that increased neuroinflammation leads to the development of depressive-like symptoms both in experimental models and humans (Lawson et al, 2013;Rosenblat et al, 2014) and administration of LPS, IL-1b or TNF-a increases immobility time in the FST (Dunn and Swiergiel, 2005;Kaster et al, 2012;Lawson et al, 2013). The mTOR pathway has also recently been indicated as a relevant pathological system implicated in major depression both in humans and experimental animal models (Cambiaghi et al, 2013;Jernigan et al, 2011;Russo et al, 2013c) and a suitable target for novel antidepressant drug development (Abelaira et al, 2014). Considering preclinical research, a major contribution has come from the recent knowledge that the rapid antidepressant effects of the general anesthetic agent ketamine are strongly associated with the activation of the mTOR pathway (Duman et al, 2012).…”

“…Considering preclinical research, a major contribution has come from the recent knowledge that the rapid antidepressant effects of the general anesthetic agent ketamine are strongly associated with the activation of the mTOR pathway (Duman et al, 2012). Inhibition of the mTOR pathway by RAP has been demonstrated to possess positive effects on animal behavior only in the case of an already underlying pathological psychiatric background and after short treatment periods (Cambiaghi et al, 2013;Russo et al, 2013c); however, we have previously demonstrated that long-term treatment with RAP both in WAG/Rij and Wistar rats increases immobility time in the FST, therefore displaying pro-depressant effects, in agreement with the suggested role of the mTOR pathway in major depression (Abelaira et al, 2014;Russo et al, 2013c).…”