Biomedical subjects

N Sherren

Publications and source records attributed to N Sherren.

4 recordsLinked to original sources

PubMed2005

Selective acetylcholine and dopamine lesions in neonatal rats produce distinct patterns of cortical dendritic atrophy in adulthood.

Acetylcholine and dopamine afferents reach their cortical targets during periods of synaptogenesis, and are in position to influence the cytoarchitectural development of cortical neurons. To determine the effect of removing these afferents on dendritic development, we lesioned rat pups at 7 days of age with the selective immunotoxins 192 IgG-saporin, or 6-hydroxydopamine, or both. One group of rats was killed in adulthood for neurochemistry and another was prepared for morphology using Golgi-Cox staining. Changes in morphology were compared in layer V pyramidal cells from medial prefrontal cortex, which sustained the greatest dopamine depletion, and in layer II/III pyramidal cells from retrosplenial cortex, which sustained the greatest choline acetyltransferase depletion. In rats with acetylcholine lesions, layer V medial prefrontal cells had smaller apical tufts and fewer basilar dendritic branches. Both apical and basilar spine density was substantially reduced. Layer II/III retrosplenial cells also had smaller apical tufts and substantially smaller basilar dendritic trees. Apical and basilar spine density did not change. In rats with dopamine lesions, layer V medial prefrontal cells had fewer oblique apical dendrites and atrophied basilar trees. Layer II/III retrosplenial cells had fewer apical dendritic branches. In neither area were spine densities significantly different from control. Neurons from rats with combined lesions were always smaller and less complex than those from singly lesioned rats. However, these cells were simple, additive composites of the morphology produced by single lesions. These data demonstrate that ascending acetylcholine and dopamine afferents play a vital role in the development of cortical cytoarchitecture.

Acetylcholine↗

PubMed2005

Neonatal lesion of forebrain cholinergic neurons: further characterization of behavioral effects and permanency.

Intraventricular injections of 192 IgG-saporin in the neonatal rat caused severe loss of basal forebrain cholinergic neurons and ectopic hippocampal ingrowths. These were evident at 24 months of age and thus, were lifelong consequences of the 192 IgG-saporin treatment. When tested as young adults on a novel water-escape radial arm maze, the rats with this lesion were slower to learn the task, committing significantly more working and reference memory errors before they achieved control level of performance. It is unlikely that this was a result of attentional impairment as the lesioned rats performed as vigilantly as controls in a five choice serial reaction time task. When tested in the Morris water maze at 22 months of age, they were slower at learning the hidden platform location. This contrasts with previous studies which have repeatedly shown that they normally acquire this task as young adults. It was concluded that this neonatal cholinergic lesion has modest but discernable effects on problem solving in young adulthood that are consistent with the reported effects of the lesion on cortical pyramidal neurons. The cognitive effects of the lesion may become more severe in aging, perhaps as a result of the added effects of aging on these neurons.

Acetylcholine↗

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↗