The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we show that LSD treatment enhanced performance in a novel object recognition task in rats, and in a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. To gain insight into the relation of neural plasticity, aging and LSD-induced cognitive gains, we emulated the experiments in rats and humans with a neural network model of a cortico-hippocampal circuit. Using the baseline strength of plasticity as a proxy for age and assuming an increase in plasticity strength related to LSD dose, the simulations provided a good fit for the experimental data. Altogether, the results suggest that LSD has nootropic effects.
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http://dx.doi.org/10.1016/j.expneurol.2022.114148 | DOI Listing |
Cell Mol Biol Lett
January 2025
PhD Program in Medical Neuroscience, Taipei Medical University, Taipei, Taiwan (R.O.C.).
Background: Regulation of messenger RNA (mRNA) transport and translation in neurons is essential for dendritic plasticity and learning/memory development. The trafficking of mRNAs along the hippocampal neuron dendrites remains translationally silent until they are selectively transported into the spines upon glutamate-induced receptor activation. However, the molecular mechanism(s) behind the spine entry of dendritic mRNAs under metabotropic glutamate receptor (mGluR)-mediated neuroactivation and long-term depression (LTD) as well as the fate of these mRNAs inside the spines are still elusive.
View Article and Find Full Text PDFNat Neurosci
January 2025
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York City, NY, USA.
Humans and animals have a striking ability to learn relationships between items in experience (such as stimuli, objects and events), enabling structured generalization and rapid assimilation of new information. A fundamental type of such relational learning is order learning, which enables transitive inference (if A > B and B > C, then A > C) and list linking (A > B > C and D > E > F rapidly 'reassembled' into A > B > C > D > E > F upon learning C > D). Despite longstanding study, a neurobiologically plausible mechanism for transitive inference and rapid reassembly of order knowledge has remained elusive.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Clinical and Experimental Epilepsy, Queen Square Institute of Neurology, UCL, London, WC1N 3BG, UK.
Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Background: Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
College of Veterinary Medicine, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address:
Rett syndrome (RTT) is a neurological disorder caused by a mutation in the X-linked methyl-CpG binding protein 2 (MECP2), leading to cognitive and motor skill regression. Therapeutic strategies aimed at increasing brain-derived neurotrophic factor (BDNF) levels have been reported; however, BDNF treatment has limitations, including the inability to penetrate the blood-brain barrier, a short half-life, and potential for adverse effects when administered via intrathecal injection, necessitating novel therapeutic approaches. In this study, we focused on the adenosine A receptor (AR), which modulates BDNF and its downstream pathways, and investigated the therapeutic potential of CGS21680, an AR agonist, through in vitro and in vivo studies using R106W RTT model.
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