MK801-induced activated caspase-3 exhibits selective co-localization with GAD67.
Blockade of the N-methyl-d-aspartate receptor (NMDAR) in postnatal day 7 (P7) rats can promote rapid and robust induction of the pro-apoptotic marker activated caspase-3 (AC3) and loss of the GABAergic marker GAD67 at P56. Thus, we hypothesized that NMDAR blockade-induced AC3 occurs in GAD67 positive cells at P7. To test this idea, we injected P7 rat pups with vehicle or MK801 and after 8h (peak of AC3 induction) we examined brain sections for both AC3 and GAD67. Compared to vehicle, MK801 profoundly induced AC3 in all brain regions examined but co-expression of GAD67 in the same cells was not observed. However, in brain regions where punctate (synaptic) GAD67 was abundant (for example, layer IV of the somatosensory cortex), AC3 was robust. These data suggest that whereas somatic expression of AC3 and GAD67 may be non-overlapping, areas that exhibit punctate GAD67 (and are high in synaptic turnover) may be more vulnerable to MK801 exposure.
Turner
Christopher P
CP
Neurobiology and Anatomy, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27157-1010, United States. cpturner@wfubmc.edu
Debenedetto
Danielle
D
Ware
Emily
E
Walburg
Caroline
C
Lee
Andrew
A
Stowe
Robert
R
Swanson
John
J
Lambert
Alexander
A
Lyle
Melissa
M
Desai
Priyanka
P
Johnson
Raymond
R
Liu
Chun
C
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005968:Glutamate Decarboxylase / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D053148:Caspase 3; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1