Neuroscience
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Focal malformations of cortical development (FMCD) are highly associated with several neurological disorders including intractable epilepsy and neurocognitive disabilities. Over the past decade, several FMCD subtypes have been linked to hyperactivation of the mammalian target of rapamycin (mTOR) signaling cascade. ⋯ These mechanisms have been directly linked to mTOR activation. Perhaps most compelling, pharmacological inhibition of mTOR has been implemented successfully in clinical trials for select FMCD and provides a new vista for treatment.
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Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and non-verbal communication, and repetitive behavior and restricted interests. Emerging evidence suggests that aberrant neuroimmune responses may contribute to phenotypic deficits and could be appropriate targets for pharmacologic intervention. ⋯ In this review, a possible pathological mechanism behind autism is proposed, which suggests that IL-6 elevation in the brain, caused by the activated glia and/or maternal immune activation, could be an important inflammatory cytokine response involved in the mediation of autism-like behaviors through impairments of neuroanatomical structures and neuronal plasticity. Further studies to investigate whether IL-6 could be used for therapeutic interventions in autism would be of great significance.
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In recent years, both major depression and antidepressant therapy have been linked to adult hippocampal neurogenesis. The hippocampus is not a homogeneous brain area, and a converging body of evidence indicates a functional dissociation along its septo-temporal axis, the dorsal part being involved more in learning/memory and spatial navigation, while the ventral sub-region is linked more to emotional behavior and regulation of the neuroendocrine stress axis. Research has therefore been conducted in an attempt to relate effects of models of depression and of antidepressant therapies to adult neurogenesis along the septo-temporal axis of the hippocampus. ⋯ Some recently introduced clinical compounds (e.g., agomelatine) or putative antidepressants have a specific action on the ventral sub-region, indicating that an action restricted to this part of the brain may be sufficient to achieve remission. Finally, non-pharmacological manipulations that are also endowed with antidepressant effects, such as environmental enrichment or physical exercise, also act on both subdivisions, although some studies pointed to specificity of dorsal neurogenesis. The different treatments, acting either on the dorsal or on the ventral sub-regions, could promote recovery by improving either ventral- or dorsal-related functions, both contributing in a different way to treatment efficacy.