title: Effects of lesions of basal forebrain cholinergic neurons in newborn rats on susceptibility to seizures.
abstract: The cholinergic system modulates cerebral excitability. We recently reported that immunolesions of the basal forebrain (BF) cholinergic neurons in adult rats increase the susceptibility to generalized seizures. In this study we investigated the effects of lesions of the BF cholinergic neurons in neonatal rats on seizure susceptibility and cognitive function. Neonatal rats at postnatal day (P) 7 received intracerebroventricular (i.c.v.) injections of 192 IgG-saporin (SAP) or phosphate-buffered saline. Following 3 weeks after the injection the first group of rats was implanted with hippocampal electrodes for electroencephalogram (EEG) recordings while the second group of rats was tested for visual spatial memory using the hidden platform version of the water maze test. The first group of rats was then tested for seizure susceptibility using flurothyl 1 week after the electrode implantation. Rats that received immunolesions of the BF cholinergic neurons at P7 had significantly shorter latencies to onset of myoclonic jerks and tonic-clonic seizures than controls. However, no significant differences were found in the duration of seizures, or EEG ictal duration. No significant deficits in spatial learning were found between rats that received i.c.v. injections of SAP at P7 and controls. As in adult rats, lesions of the BF cholinergic system in rat pups result in subsequent increase in seizure susceptibility.
authors.affiliation: Department of Neurology, Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Enders # 320, Boston, MA 02155, USA. diosely.silveira@tch.harvard.edu
authors.forename: Diosely C
authors.initials: DC
authors.lastname: Silveira
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Cha
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D020532:Basal Nucleus of Meynert / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000378:metabolism*; D004198:Disease Susceptibility / Q000378:metabolism* / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D000922:Immunotoxins; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology; D009699:N-Glycosyl Hydrolases; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009434:Neural Pathways / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine