Chemogenetics: Beyond Lesions and Electrodes

Poth, Kelly M.; Texakalidis, Pavlos; Boulis, Nicholas M.

doi:10.1093/neuros/nyab147

Cited by 21 publications

(23 citation statements)

References 109 publications

(143 reference statements)

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“…Optical fibers can also be integrated with advanced spinal endoscopes (white light and fluorescence) to complete molecular image-guided BSCB opening (29, 30). Furthermore, Opto-BSCB also has the potential to be used for studying neuromodulation in combination with chemogenetics (31) or optogenetics (16).…”

Section: Discussionmentioning

confidence: 99%

Minimally invasive delivery of peptides to the spinal cord for behavior modulation

Gao

David

Leong

et al. 2022

Preprint

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The blood-spinal cord barrier (BSCB) tightly regulates molecular transport from the blood to the spinal cord. Herein, we present a novel approach for transient modulation of BSCB permeability and localized delivery of peptides into the spinal cord for behavior modulation with high spatial resolution. This approach utilizes optical stimulation of vasculature-targeted nanoparticles and allows delivery of BSCB-nonpermeable molecules into the spinal cord without significant glial activation or impact on animal locomotor behavior. We demonstrate minimally invasive light delivery into the spinal cord using an optical fiber and BSCB permeability modulation in the lumbar region. Our method of BSCB modulation allows delivery of bombesin, a centrally-acting and itch-inducing peptide, into the spinal cord and induces a rapid and transient increase in itching behaviors in mice. This minimally invasive approach enables behavior modulation without genetic modifications and is promising for delivering a wide range of biologics into the spinal cord for behavior modulation and potentially therapy.Significance StatementSpinal cord diseases and disorders are common and cause significant disability, including chronic pain, paralysis, cognitive impairment, and mortality. The blood-spinal cord barrier is a considerable challenge for delivery by systemic therapeutic administration. We developed an optical approach for effectively and safely delivering molecules to the spinal cord to overcome this barrier. The fiberoptic method is minimally invasive and overcomes challenges that previous technologies face, including the complicated bone structure and standing waves that complicate BSCB opening using ultrasound. Optical stimulation offers unprecedented spatial resolution for the precise delivery in intricate spinal cord structures. Significantly, our approach modulates animal behavior (i.e., itch) without genetic modifications and demonstrates the potential for delivery of biologics such as peptides into the spinal cord.

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Section: Discussionmentioning

confidence: 99%

Minimally invasive delivery of peptides to the spinal cord for behavior modulation

Gao

David

Leong

et al. 2022

Preprint

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“…The murine model strongly benefited from the invention of the Cre-loxP system, which allows for cell-specific modifications targeting skin, immune, and brain cells [102]. In addition, chemogenetics and optogenetics provide the opportunity of remote-controling neural activity (facilitation or silencing, respectively) at a higher spatial resolution than ever before in cells of interest [103]. In the case of chemogenetics, DREADD (Designer Receptors Exclusively Activated by Designer Drugs) constructs are transferred to cells by viral vectors.…”

Section: Interventional Approachesmentioning

confidence: 99%

“…In the case of chemogenetics, DREADD (Designer Receptors Exclusively Activated by Designer Drugs) constructs are transferred to cells by viral vectors. The then-expressed engineered proteins interact with previously biological inactive small molecules, allowing for a time-restricted modification of cellular activity [103]. Optogenetics offers an even more precise temporal resolution by inhibiting or activating the neural activity in specific brain regions in response to light via expressing light-sensitive ion channels, pumps, or enzymes [104].…”

Section: Interventional Approachesmentioning

confidence: 99%

Probing the Skin–Brain Axis: New Vistas Using Mouse Models

Weiglein

Gaffal

Albrecht

2022

IJMS

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Inflammatory diseases of the skin, including atopic dermatitis and psoriasis, have gained increasing attention with rising incidences in developed countries over the past decades. While bodily properties, such as immunological responses of the skin, have been described in some detail, interactions with the brain via different routes are less well studied. The suggested routes of the skin–brain axis comprise the immune system, HPA axis, and the peripheral and central nervous system, including microglia responses and structural changes. They provide starting points to investigate the molecular mechanisms of neuropsychiatric comorbidities in AD and psoriasis. To this end, mouse models exist for AD and psoriasis that could be tested for relevant behavioral entities. In this review, we provide an overview of the current mouse models and assays. By combining an extensive behavioral characterization and state-of-the-art genetic interventions with the investigation of underlying molecular pathways, insights into the mechanisms of the skin–brain axis in inflammatory cutaneous diseases are examined, which will spark further research in humans and drive the development of novel therapeutic strategies.

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“…Unlike other stimulogenetic strategies, it does not require specialized instruments to function. The poor temporal resolution in chemogenetics could be a boon in studying those disease processes which are independent of modulation on the millisecond time scale [ 18 ]. However, the spatial resolution of chemogenetics is poor, as the artificial ligand might modulate other genetically similar cell receptors.…”

Section: The Stimulogenetics Toolkitmentioning

confidence: 99%

Introducing stimulogenetics, unraveling pertinent semantic ambiguity, and determining clinical relevance among novel neuromodulation strategies

Garg

Muthiah²,

Sengupta

2022

Biology Methods and Protocols

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Deep Brain Stimulation involving the stereotactic implantation of electrodes in the deeper neural tissue remains one of the most trusted non-pharmacotherapeutic approaches for neuromodulation in the clinical setting. The recent advent of techniques that can modulate the neural structure and/or function at the cellular level has stimulated the exploration of these strategies in managing neurological and psychiatric disorders. Optogenetics, which is widely employed in experimental research, is the prototype of the above techniques. Other methods, such as chemogenetics, sonogenetics, and magnetogenetics have also been introduced. Although these strategies possess several noticeable differences, they have an overlapping conceptual framework enabling their classification under a singular hypernym. This paper introduces this hypernym, ′stimulogenetics′ in an attempt to solve the pertinent ambiguity to aid the classification of existing literature. The paper also compares the strategies classified under stimulogenetics and concludes that the current literature suggests that non-invasive approaches such as chemogenetics and sonogenetics are better suited for clinical applications. However, due to the dearth of clinical studies, it is not possible to determine this definitively.

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Chemogenetics: Beyond Lesions and Electrodes

Cited by 21 publications

References 109 publications

Minimally invasive delivery of peptides to the spinal cord for behavior modulation

Minimally invasive delivery of peptides to the spinal cord for behavior modulation

Probing the Skin–Brain Axis: New Vistas Using Mouse Models

Introducing stimulogenetics, unraveling pertinent semantic ambiguity, and determining clinical relevance among novel neuromodulation strategies

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