N Sherren | PubMed Health

PubMed2000

Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion.

Adult rats who have undergone neonatal 192 IgG-saporin induced lesions of forebrain acetylcholine (ACH) neurons are normal on many behavioral tasks. In this study we determined whether ectopic hippocampal ingrowths, a documented consequence of these neonatal cholinergic lesions, functionally compensate for ACH denervation in these rats. Neonatal rats underwent systemic 6-hydroxydopamine (6-OHDA) injections on postnatal days (PND) 1-3 to prevent the ingrowths, and/or intraventricular 192 IgG-saporin injections on PND 7. The 192 IgG-saporin profoundly reduced basal forebrain p75 neurotrophin receptor (p75(NTR)) immunoreactive (IR) neurons. The 6-OHDA treatment abolished hippocampal and cortical dopamine-beta-hydroxylase (DBH) IR terminals, indicating the absence of normal norepinephrine (NE) innervation. Ectopic DBH IR and p75(NTR) IR varicosities which occurred in the hippocampus of 192 IgG-saporin treated rats were also eliminated by 6-OHDA treatment. Behavioral testing in adulthood indicated no effect of the treatments on the Morris water maze. 192 IgG-saporin treatment caused perseveration during delayed spatial alternation (DSA) and increased working but not reference memory errors on the radial arm maze (RAM). The 6-OHDA plus 192 IgG-saporin treated rats did not differ from the 192 IgG-saporin only rats on any task. These results indicate that ectopic hippocampal NE ingrowths do not functionally compensate for neonatal ACH lesions. Neonatal forebrain ACH lesion impairs working memory on the RAM but the absence of an effect on DSA contraindicates a basic dysfunction of short term memory. Despite severe combined neonatal loss of forebrain ACH and NE innervation, behavior is remarkably intact.

Acetylcholine↗

PubMed1999

Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects?

The consequences of neonatal cholinergic lesions were examined in male and female rats. Rats were injected intraventricularly with 600 ng of 192 IgG-saporin at 7 days of age and examined behaviorally and histologically at 21, 45 and 90 days of age. 192 IgG-saporin profoundly reduced low affinity neurotrophin receptor (p75NTR)-immunoreactive (IR) and, to a lesser extent, choline acetyltransferase-IR cells in the basal forebrain. Presumptive sympathetic ingrowths (p75NTR- and dopamine beta-hydroxylase-IR) into the hippocampus were first apparent at 45 days of age and were not significantly greater at 90 days. Behaviorally, 192 IgG-saporin increased the time females, but not males, spent on the open arms of the elevated plus maze. Lesioned rats had longer platform location latencies in the Morris water maze only at the first hidden platform training session and did not differ on the rate of learning the platform location or on the no-platform probe trial. Generally, the effects of neonatal cholinergic lesions were not sex dependent and are unlikely to model Rett syndrome, a disorder characterized by forebrain cholinergic deficit which is seen almost exclusively in females.

Acetylcholine↗