Duncan Banks

Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm

Colostrinin (CLN) is a biologically active proline-rich polypeptide which has therapeutic potential for the alleviation of memory deficits in age-related dementias in a number of human conditions, particularly Alzheimers disease. To examine the efficacy of CLN in other species, day-old domestic chicks were used as a model system to study its effects on retention of memory for a single one-trial learning paradigm--avoidance of a bitter-tasting substance (methylanthranilate, MeA). Birds were presented with a bead coated with either a dilute (10%) solution of MeA or a bead coated with 100% MeA. Those trained on 100% MeA avoided pecking at a similar but dry bead 24 h later, thereby demonstrating long-term memory whereas chicks trained on the 10% solution pecked the bead at 24 h, indicating lack of long term memory for the task. However, when CLN was injected (i.c.) into a region known to be important in memory formation, the mesopallium intermediomediale (IMM), prior to training with 10% MeA, chicks exhibited strong memory retention at 24 h, similar to those trained on 100% MeA. Control chicks trained on 10% MeA but injected i.c. with a 10% saline solution did not show improvement in memory retention. Intraperitoneal (i.p.) injections of CLN were as effective as the i.c. route. These data extend the known efficacy of CLN from mammals demonstrating its widespread efficacy as a cognitive enhancer.

Colostrinin™ Alleviates Amyloid-β Induced Toxicity in Rat Primary Hippocampal Cultures

Colostrinin (CLN), a complex mixture of proline-rich polypeptides derived from colostrums, can alleviate cognitive decline in early Alzheimers disease patients. The molecular basis of the action of CLN has been studied in vitro using human neuroblastoma cell lines. The aim of the present study was to use quantitative immunocytochemistry and immunoblotting to investigate the ability of CLN to relieve amyloid-beta (Abeta)-induced cytotoxicity in rat primary hippocampal neuronal cells. Our data confirm that CLN alleviates the effect of Abeta-induced cytotoxicity and causes a significant reduction in the elevated levels of the antioxidant enzyme SOD1.

Safety of medicines and the use of animals in research

www.thelancet.com Vol 378 July 9, 2011 127 The issue of teratogenic potential of topiramate raised by Pieter Cohen is an evolving one with emerging data. The FDA’s concern in this regard seems to have been heightened by an abstract which describes data from the North American Antiepileptic Drug Pregnancy Registry and showed that major malformations occurred signifi cantly more often in topiramate-exposed pregnancies than in the unexposed (3·8% vs 1·3%, relative risk 2·8, 95% CI 1·0–8·1); cleft lip occurred in four (1·4%) of 289 infants exposed to topiramate (two cases [0·69%] were isolated)—a rate markedly higher than the expected prevalence of isolated cleft lip of 0·07%. These results have been, at least in part, contradicted by a more recent population-based cohort study of 837 795 liveborn infants in Denmark over a 13-year span. This report estimated the adjusted prevalence odds ratio (compared with infants not exposed to any antiepileptic drug) for major malformations in infants exposed to topiramate during pregnancy as 1·44 (95% CI 0·58–3·58). In our study, participants had two or more obesity-associated comorbid ities and treatment with phentermine plus topiramate led to improvements in lipids, glycaemic control, systolic blood pressure, and infl ammatory markers, pointing to a positive benefi t:risk ratio. Careful risk mitigation plans could assure that patients for whom it is inappropriate are not prescribed the drug, while those who might benefi t most are allowed access.

Three-dimensional ultrastructural and immunohistochemical study of immature neurons in the subgranular zone of the rat dentate gyrus

The present study is devoted to three-dimensional ultrastructural organization of mitotically dividing immature neurons in dentate gyrus using biophysical approaches. In adult vertebrate brain, cell proliferation persists throughout life mainly in dentate gyrus of the hippocampus (DG) and olfactory bulb. Neurogenesis has been demonstrated using tagged thymidine analogues incorporated into the S phase of the cell cycle, but these may also detect repaired DNA in postmitotic neurons. Recent retroviral labelling has shown that neuronal progenitors/neuroblasts divide and produce functional neurons. Providing ultrastructural evidence of mitotically active cells has proven problematical, not only because of technical issues of identifying dividing cells at electron microscope level, but also because it is difficult to demonstrate unequivocally that neurons identified in the electron microscope are really post mitotic. However by characterising post mitotic cells labelled with BrdU and doublecortin and comparing these with post mitotic cells reconstructed in 3-dimensions from ultrathin serial sections, we have been able to illustrate individual mitotic elements and phases of cells within the GC layer of adult rat dentate gyrus. Here we show dividing cells in metaphase within clusters of immature GCs in subgranular zone (SGZ). These reconstructions provide ultrastructural confirmation that cells expressing doublecortin (DCX), a microtubule-associated protein expressed in migrating neurons, localize as clusters in the subgranular zone (SGZ) of dentate gyrus (DG) in the hippocampus during all animal life. Such DG cells with clear synaptic specializations, somatic spines and basal dendrites are exclusive to immature GC that appear to re-enter the cell cycle, suggesting the possibility that newly generated neurons within the DG might arise not only from precursors, but also from clusters of immature GC.