Prefrontal cortex neural compensation during an operant devaluation task

Deficits in goal-directed action are reported in multiple neuropsychiatric conditions, including schizophrenia. However, dysfunction is not always apparent in early stages of schizophrenia, possibly due to neural compensation. We designed a novel devaluation task in which goal-directed action could be guided by stimulus-outcome (S-O) [presumably orbitofrontal cortex (OFC)-mediated] or response-outcome (R-O) associations [presumably prelimbic cortex (PL)-mediated]. We previously found suggestive evidence that OFC and PL could compensate for each other in this task, and we more directly assessed this potential compensation here. In Experiment 1, rats received OFC, PL, combined OFC+PL, or sham lesions and then completed our devaluation task. The OFC+PL lesion group exhibited impaired devaluation. In Experiment 2, rats received cholera-toxin-b (CTb) into OFC and either neurotoxic or sham PL lesions. Rats were then sacrificed on the last training day to double-label for Arc and CTb. We found increased Arc+CTb in mediodorsal thalamus (MD) and increased Arc+ neurons in OFC when PL was lesioned, suggesting that PL lesions lead to a compensatory increased activation of the MD->OFC circuit. Our results suggest that our devaluation task can model neural compensation between OFC and PL and this compensation may be regulated by MD.

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Dynamin-mediated Internalization of Caveolae

The Journal of Cell Biology ◽

10.1083/jcb.141.1.85 ◽

1998 ◽

Vol 141 (1) ◽

pp. 85-99 ◽

Cited By ~ 526

Author(s):

John R. Henley ◽

Eugene W.A. Krueger ◽

Barbara J. Oswald ◽

Mark A. McNiven

Keyword(s):

Mammalian Cells ◽

Immunofluorescence Microscopy ◽

In Vivo Studies ◽

Coated Pits ◽

Toxin B ◽

Cholera Toxin B ◽

Double Label ◽

Biochemical Analyses ◽

Redundant Functions

The dynamins comprise an expanding family of ubiquitously expressed 100-kD GTPases that have been implicated in severing clathrin-coated pits during receptor-mediated endocytosis. Currently, it is unclear whether the different dynamin isoforms perform redundant functions or participate in distinct endocytic processes. To define the function of dynamin II in mammalian epithelial cells, we have generated and characterized peptide-specific antibodies to domains that either are unique to this isoform or conserved within the dynamin family. When microinjected into cultured hepatocytes these affinity-purified antibodies inhibited clathrin-mediated endocytosis and induced the formation of long plasmalemmal invaginations with attached clathrin-coated pits. In addition, clusters of distinct, nonclathrin-coated, flask-shaped invaginations resembling caveolae accumulated at the plasma membrane of antibody-injected cells. In support of this, caveola-mediated endocytosis of labeled cholera toxin B was inhibited in antibody-injected hepatocytes. Using immunoisolation techniques an anti-dynamin antibody isolated caveolar membranes directly from a hepatocyte postnuclear membrane fraction. Finally, double label immunofluorescence microscopy revealed a striking colocalization between dynamin and the caveolar coat protein caveolin. Thus, functional in vivo studies as well as ultrastructural and biochemical analyses indicate that dynamin mediates both clathrin-dependent endocytosis and the internalization of caveolae in mammalian cells.

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Oral administration to NOD mice of diabetic autoantigens: Pure and linked to cholera toxin B subunit

Immunology Letters ◽

10.1016/s0165-2478(97)88813-x ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 484

Author(s):

I Bache

Keyword(s):

Oral Administration ◽

Cholera Toxin ◽

Nod Mice ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit

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Purification and Analysis of a Recombinant Human Anti-Cholera Toxin B Antibody.

10.21236/ada341970 ◽

1998 ◽

Author(s):

Jessica Dang ◽

Suzanne Kracke ◽

Peter A. Emanuel ◽

Michael J. Gostomski ◽

Darrel E. Menking

Keyword(s):

Cholera Toxin ◽

Toxin B ◽

Cholera Toxin B

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Spray-Dried Formulation of Epicertin, a Recombinant Cholera Toxin B Subunit Variant That Induces Mucosal Healing

Pharmaceutics ◽

10.3390/pharmaceutics13040576 ◽

2021 ◽

Vol 13 (4) ◽

pp. 576

Author(s):

Micaela A. Reeves ◽

Joshua M. Royal ◽

David A. Morris ◽

Jessica M. Jurkiewicz ◽

Nobuyuki Matoba ◽

...

Keyword(s):

Gastric Acid ◽

Cholera Toxin ◽

Oral Formulation ◽

Size Exclusion ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit ◽

Enteric Coated ◽

Spray Dried

Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit, modified with a C-terminal KDEL endoplasmic reticulum retention motif. EPT has therapeutic potential for ulcerative colitis treatment. Previously, orally administered EPT demonstrated colon epithelial repair activity in dextran sodium sulfate (DSS)-induced acute and chronic colitis in mice. However, the oral dosing requires cumbersome pretreatment with sodium bicarbonate to conserve the acid-labile drug substance while transit through the stomach, hampering its facile application in chronic disease treatment. Here, we developed a solid oral formulation of EPT that circumvents degradation in gastric acid. EPT was spray-dried and packed into enteric-coated capsules to allow for pH-dependent release in the colon. A GM1-capture KDEL-detection ELISA and size-exclusion HPLC indicated that EPT powder maintains activity and structural stability for up to 9 months. Capsule disintegration tests showed that EPT remained encapsulated at pH 1 but was released over 180 min at pH 6.8, the approximate pH of the proximal colon. An acute DSS colitis study confirmed the therapeutic efficacy of encapsulated EPT in C57BL/6 mice upon oral administration without gastric acid neutralization pretreatment compared to vehicle-treated mice (p < 0.05). These results provide a foundation for an enteric-coated oral formulation of spray-dried EPT.

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