Experimental Neurology
June 1, 2022
I. Ornelas, F. A. Cini, Isabel Wießner et al.
37 citations
LSD treatment improved performance in a novel object recognition task in rats and 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. Simulations using a neural network model of a cortico-hippocampal circuit, with baseline plasticity strength as a proxy for age and increased plasticity related to LSD dose, fit the experimental data well. The results suggest that LSD has nootropic effects.
bioRxiv (Cold Spring Harbor Laboratory)
December 6, 2019
Felipe Augusto Cini da Silva, Isis M. Ornelas, Encarni Marcos et al.
9 citations
preprint
A single dose of d-LSD, a potent serotonergic agonist, increased preference for novel objects in young and adult rats several days after treatment, but did not increase preference in old animals unless followed by a 6-day exposure to enriched environment, which rescued novelty preference to young levels. Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions with alterations of long-range synapses, and that better pattern separation within enriched environment explains its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.
ACS Omega
August 27, 2024
Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento et al.
3 citations
Exposure to LSD alters the abundance of hundreds of proteins in lab-grown human brain tissue, affecting pathways related to protein quality control, energy metabolism, and the brain's ability to rewire itself. Mass spectrometry revealed changes in protein synthesis, folding, and degradation, as well as in glycolysis and oxidative phosphorylation. Follow-up experiments showed that LSD also promotes the growth of neuronal extensions, supporting its influence on neuroplasticity. These molecular changes may help explain how psychedelics could produce therapeutic effects in neuropsychiatric disorders.
bioRxiv Preprint Server
January 30, 2024
Marcelo N. Costa, Livia Goto-Silva, Juliana Nascimento et al.
1 citation
preprint
Proteomic analysis of human cerebral organoids reveals that lysergic acid diethylamide (LSD) alters proteins involved in proteostasis, energy metabolism, and neuroplasticity-related pathways. LSD exposure changed protein synthesis, folding, autophagy, and proteasomal degradation, suggesting complex regulation of neural cell function. It also modulated glycolysis and oxidative phosphorylation, which are crucial for cellular energy management and synaptic function. Complementary experiments showed LSD enhanced neurite outgrowth in vitro, confirming its impact on neuroplasticity. These findings provide insight into molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.
bioRxiv (Cold Spring Harbor Laboratory)
June 17, 2021
Karina Karmirian, Livia Goto-Silva, Juliana Nascimento et al.
1 citation
preprint
Harmine, a β-carboline found in the ayahuasca vine Banisteriopsis caapi, upregulates proteins in human brain organoids that are involved in synaptic vesicle cycling, cytoskeleton-dependent transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling. Treatment with harmine also increased levels of Akt and phosphorylated CREB after 24 hours. These findings point to cellular and molecular pathways that may explain harmine's potential neuroprotective effects, which have been suggested by previous animal studies to include anti-inflammatory and antioxidant activities. The work advances understanding of how harmine might contribute to the antidepressant effects observed with ayahuasca.