Investigation of how stimulation intensity of rTMS affects magneto permeabilization of the Blood–Brain Barrier (BBB)

Afkham, Behrouz Vejdani; Shankayi, Zeinab; Bahrami, Fariba; Firoozabadi, Seyed Mohammad; Heydarheydari, Sahel; Mohammadi, Mohammad Taghi

doi:10.1080/15368378.2022.2095644

Cited by 1 publication

(1 citation statement)

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“…In addition, improved efficacy could be obtained by increasing the directional flow of cargo following intranasal delivery. Techniques that could be applied in this manner include pulsed ultrasound and transcranial magnetic stimulation ( 57 , 58 ). Delivery within the CNS was accomplished using a noninvasive intranasal delivery platform that can bypass the BBB, typically a major hurdle for large cargo such as CRISPR/Cas9.…”

Section: Discussionmentioning

confidence: 99%

Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice

et al. 2023

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The expanding field of precision gene editing using CRISPR/Cas9 has demonstrated its potential as a transformative technology in the treatment of various diseases. However, whether this genome-editing tool could be used to modify neural circuits in the central nervous system (CNS), which are implicated in complex behavioral traits, remains uncertain. In this study, we demonstrate the feasibility of noninvasive, intranasal delivery of adeno-associated virus serotype 9 (AAV9) vectors containing CRISPR/Cas9 cargo within the CNS resulting in modification of the HTR2A receptor gene. In vitro, exposure to primary mouse cortical neurons to AAV9 vectors targeting the HT2RA gene led to a concentration-dependent decrease in spontaneous electrical activity following multielectrode array (MEA) analysis. In vivo, at 5 weeks postintranasal delivery in mice, analysis of brain samples revealed single base pair deletions and nonsense mutations, leading to an 8.46-fold reduction in mRNA expression and a corresponding 68% decrease in the 5HT-2A receptor staining. Our findings also demonstrate a significant decrease in anxiety-like behavior in treated mice. This study constitutes the first successful demonstration of a noninvasive CRISPR/Cas9 delivery platform, capable of bypassing the blood–brain barrier and enabling modulation of neuronal 5HT-2A receptor pathways. The results of this study targeting the HTR2A gene provide a foundation for the development of innovative therapeutic strategies for a broad range of neurological disorders, including anxiety, depression, attentional deficits, and cognitive dysfunction.

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Section: Discussionmentioning

confidence: 99%