Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :30082415
Publication Date : //

Behavioral Effect of Chemogenetic Inhibition Is Directly Related to Receptor Transduction Levels in Rhesus Monkeys.


We used inhibitory DREADDs (designer receptors exclusively activated by designer drugs) to reversibly disrupt dorsolateral prefrontal cortex (dlPFC) function in male rhesus monkeys. Monkeys were tested on a spatial delayed response task to assess working memory function after intramuscular injection of either clozapine--oxide (CNO) or vehicle. CNO injections given before DREADD transduction were without effect on behavior. rAAV5/hSyn-hM4Di-mCherry was injected bilaterally into the dlPFC of five male rhesus monkeys, to produce neuronal expression of the inhibitory (Gi-coupled) DREADD receptor. We quantified the percentage of DREADD-transduced cells using stereological analysis of mCherry-immunolabeled neurons. We found a greater number of immunolabeled neurons in monkeys that displayed CNO-induced behavioral impairment after DREADD transduction compared with monkeys that showed no behavioral effect after CNO. Even in monkeys that showed reliable effects of CNO on behavior after DREADD transduction, the number of prefrontal neurons transduced with DREADD receptor was on the order of 3% of total prefrontal neurons counted. This level of histological analysis facilitates our understanding of behavioral effects, or lack thereof, after DREADD vector injection in monkeys. It also implies that a functional silencing of a relatively small fraction of dlPFC neurons, albeit in a widely distributed area, is sufficient to disrupt spatial working memory. Cognitive domains such as working memory and executive function are mediated by the dorsolateral prefrontal cortex (dlPFC). Impairments in these domains are common in neurodegenerative diseases as well as normal aging. The present study sought to measure deficits in a spatial delayed response task following activation of viral-vector transduced inhibitory DREADD (designer receptor exclusively activated by designer drug) receptors in rhesus macaques and compare this to the level of transduction in dlPFC using stereology. We found a significant relationship between the extent of DREADD transduction and the magnitude of behavioral deficit following administration of the DREADD actuator compound clozapine--oxide (CNO). These results demonstrate it will be critical to validate transduction to ensure DREADDs remain a powerful tool for neuronal disruption.

Authors : Upright Nicholas A , Brookshire Stephen W , Schnebelen Wendy , Damatac Christienne G , Hof Patrick R , Browning Philip G F , Croxson Paula L , Rudebeck Peter H , Baxter Mark G ,

Related products :

Catalog number Product name Quantity
25-763 Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. 0.05 mg
28-708 ZHX2 a zinc fingers and homeoboxes (ZHX) protein that is directly involved in the regulation of AFP synthesis. It also controls AFP levels only indirectly, e.g., by regulating the synthesis of a hormo 0.1 mg
PY-10177 Signal transduction related antibodies: Anti-tumor necrosis factor receptor superfamily, member 6 isoform 1(FAS),Chicken-Poly 100μg
27-963 ARHGDIG is highly expressed in the entire brain, with regional variations. The mRNA is also present at high levels in kidney and pancreas and at moderate levels in spinal cord, stomach, and pituitary 0.05 mg
25-176 CCRL2 is a chemokine receptor like protein, which is predicted to be a seven transmembrane protein and most closely related to CCR1. Chemokines and their receptors mediated signal transduction are cri 0.05 mg
30-397 RSU1 is a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line stud 0.1 mg
MR-003 ///NEW Antibody 2-Step Effect Universal Anti-Mouse_ Anti-Rabbit IgG 2-Step Effect Universal 50ml
MR-003 ///NEW Antibody 2-Step Effect Universal Anti-Mouse_ Anti-Rabbit IgG 2-Step Effect Universal 100ml
29-786 EDG8 is a receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. It Is coupl 0.05 mg
29-785 EDG8 is a receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. It Is coupl 0.1 mg
GIDRP_MOUSE ELISA Kit FOR Growth inhibition and differentiation-related protein 88 homolog; organism: Mouse; gene name: Gidrp88 96T
32-231 TRIM5-alpha is a protein that is found in the cells of many mammals and fends of various retrovirus infections. It protects monkeys from infection with HIV-1, and humans from infection with some other 0.1 mL
EIAAB38456 Homo sapiens,Human,SIGIRR,Single Ig IL-1-related receptor,Single Ig IL-1R-related molecule,Single immunoglobulin domain-containing IL1R-related protein,TIR8,Toll_interleukin-1 receptor 8,UNQ301_PRO342
EIAAB38457 Rat,Rattus norvegicus,Sigirr,Single Ig IL-1-related receptor,Single Ig IL-1R-related molecule,Single immunoglobulin domain-containing IL1R-related protein,TIR8,Toll_interleukin-1 receptor 8
31-089 The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing). 0.05 mg
31-090 The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing). 0.1 mg
18-661-15202 Single Ig IL-1-related receptor - Single Ig IL-1R-related molecule; Single immunoglobulin domain-containing IL1R-related protein; Toll_interleukin-1 receptor 8; TIR8 Polyclonal 0.1 mg
PY-10185 Signal transduction related antibodies: Anti-STAT6,Chicken-Poly 100μg
PY-10072 Signal transduction related antibodies: Anti-CD34,Chicken-Poly 100μg
25-696 HSD11B2 catalyzes the conversion of cortisol to the inactive metabolite cortisone. It modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from oc 0.05 mg
EIAAB13287 Errg,Esrrg,Estrogen receptor-related protein 3,Estrogen-related receptor gamma,Nr3b3,Nuclear receptor subfamily 3 group B member 3,Rat,Rattus norvegicus
EIAAB13288 Err3,Esrrg,Estrogen receptor-related protein 3,Estrogen-related receptor gamma,Kiaa0832,Mouse,Mus musculus,Nr3b3,Nuclear receptor subfamily 3 group B member 3
orb81121 Human Fibronectin protein Plasma fibronectin level is elevated in severe coronary artery disease. Increased plasma fibronectin levels are related with venous thromboembolism (VTE) particularly in male 200
PY-10184 Signal transduction related antibodies: Anti-STAT1 beta,Chicken-Poly 100μg
PY-10198 Signal transduction related antibodies: Anti- Jun kinase(JNK2),Chicken-Poly 100μg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur | Gentaur





GENTAUR Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
france@gentaur.com | Gentaur | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: +49 0241 40 08 90 86, +49 0241 95 78 94 78, +49 0241 40 08 90 86
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur | Gentaur