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Biomedical subjects

Susan A Farr

Publications and source records attributed to Susan A Farr.

22 records · Page 2Linked to original sources

Blind mice are not impaired in T-maze footshock avoidance acquisition and retention.

The processing of visual information during learning and memory is considered to be a vital function of the hippocampus. Some researchers believe that the sole purpose of the hippocampus is to process visuo-spatial information, whereas other investigators believe that the hippocampus integrates cues from multiple sources. In the current studies, we tested the effects of vision loss on a hippocampal task, acquisition and retention with T-maze footshock avoidance conditioning. Acquisition and retention, in adult-blinded mice, were not significantly impaired in T-maze footshock avoidance. Blindness did not affect activity, footshock startle or motivation to avoid shock. The same doses of memory enhancing drugs that improve memory in sighted mice improved memory in blind mice. Electrolytic lesions in blind mice, which destroyed 31+/-4% of the hippocampus, significantly impaired acquisition and retention for T-maze footshock avoidance and so demonstrated that the hippocampus retained its integrative role in blind mice. The current findings show that blind mice are as capable of learning T-maze footshock avoidance as sighted mice and that the hippocampus retains its important role in blind mice in learning and memory processing. It is concluded that the T-maze footshock avoidance conditioning task is a spatially but not visually dependent task that is hippocampally dependent.

Acoustic Stimulation↗

Effects of orexin-A on memory processing.

Orexin-A is an endogenous peptide with receptors present throughout the brain. Here, we examined the effect of post-training administration of orexin-A on retention in active and passive avoidance. Orexin-A administered by intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved retention in both T-maze footshock avoidance and one trial step-down passive avoidance. SAMP8 mice have age-related deficits in learning and memory, which correlate with an increase in brain levels of beta amyloid (Abeta) and an impaired response to memory-enhancing compounds. Orexin-A at 3nmol improved retention in young and old SAMP8 mice. These findings show that orexin-A can improve memory even with overproduction of Abeta.

Amyloid beta-Peptides↗

Passage of amyloid beta protein antibody across the blood-brain barrier in a mouse model of Alzheimer's disease.

Vaccinations against amyloid beta protein (A beta P) reduce amyloid deposition and reverse learning and memory deficits in mouse models of Alzheimer's disease. This has raised the question of whether circulating antibodies, normally restricted by the blood-brain barrier (BBB), can enter the brain [Nat. Med. 7 (2001) 369-372]. Here, we show that antibody directed against A beta P does cross the BBB at a very low rate. Entry is by way of the extracellular pathways with about 0.11% of an intravenous (i.v.) dose entering the brain by 1h. Clearance of antibody from brain increasingly dominates over time, but antibody is still detectable in brain 72 h after i.v. injection. Uptake and clearance is not altered in mice overexpressing A beta P. This ability to enter and exit the brain even in the presence of increased brain ligand supports the use of antibody in the treatment of Alzheimer's and other diseases of the brain.

Aging↗

Entry of blood-borne cytokines into the central nervous system: effects on cognitive processes.

Blood-borne cytokines affect many aspects of the central nervous system (CNS). One of the more dramatic effects is the induction of sickness behavior. Impairments in learning and memory are an important component of sickness behavior and are largely mediated by IL-1. Many mechanisms have been proposed by which a cytokine circulating in the blood can affect functions within the CNS. We review here the role one of those mechanisms, that of transport of cytokines across the blood-brain barrier (BBB), plays in induction of the memory impairments of sickness behavior. We have shown that the posterior division of the septum (PDS) plays a key role in mediating the effects of interleukin-1alpha (IL-1alpha) on memory. Furthermore, this effect at the PDS is largely mediated by circulating IL-1alpha acting directly at the PDS which, in turn, depends on the ability of IL-1alpha to cross the BBB.

Animals↗