Reversal of early phenobarbital-induced cholinergic and related behavioral deficits by neuronal grafting.
The present experiment was performed to assess the possible restoration of normal maze behavior, as well as parallel muscarinic receptor binding capabilities, in mice pre- or neonatally exposed to phenobarbital. Mice were exposed to phenobarbital prenatally by feeding the mother phenobarbital (3 gkg milled food) on gestation days 9-18 (PreB mice), or neonatally, by daily injections of 50 mg/kg Na phenobarbital to the pups on days 2-21 (NeoB). At adulthood, PreB and NeoB mice were 61.3% and 65% deficient, respectively, in the hippocampus-related Morris maze behavior, as compared to control. Both groups had a 58% increase in their hippocampal muscarinic receptors maximal binding (Bmax) (p < 0.001); the dissociation constant (Kd) was not affected by the phenobarbital exposure. Treated animals and their respective controls received septal cholinergic embryonic graft into the hippocampus. The viability of the transplants was confirmed by AChE histochemistry. Nine weeks later the grafted mice showed significant improvement in the Morris maze (52% for both PreB and NeoB (p < 0.001)). Their Bmax was also reduced from early phenobarbital exposed animals' levels by 15% for PreB and by 25% for NeoB (p < 0.001). The results suggest that early phenobarbital-induced behavioral deficit and their related biochemical alterations can be partially corrected by the appropriate neural grafting, and thus provide further support to the apparent relationship between the early phenobarbital-induced septohippocampal cholinergic alterations and the hippocampus-related behavioral deficits.
Rogel-Fuchs
Y
Y
Melvin A. and Eleanor Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Zahalka
E A
EA
Yanai
J
J
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000637:transplantation*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011976:Receptors, Muscarinic / Q000378:metabolism
D011976:Receptors, Muscarinic; D000110:Acetylcholinesterase; D010634:Phenobarbital