Comparative analysis of dentate gyrus from naive Wistar rats and human hippocampus using molecular tools

Much of the studies related to the hippocampus are aimed to elucidate the diseases which affect this structure, such as Mesial Temporal Lobe Epilepsy (MTLE) and Alzheimer’s disease (AD). However, to better understand the pathophysiology of these diseases, which are not fully elucidated, we must focus in other structures from the Hippocampal Formation, that can be involved with these mechanisms, such as the DG¹. The DG itself is also subdivided into dorsal and ventral in rodents and posterior and anterior in humans². Moreover, the neurodegenerative diseases, as others, are usually investigated using animal models, mainly rodents, due to its possibility of study the development of the diseases and not only its final stage³. However, despite its remarkable similarities with humans, it is necessary to evaluate the differences between the two species to validate the rodents as a suitable model for human pathologies. Therefore, here we present the comparative multi-OMICs analysis of the laser microdissected DG from rat and humans, intending to characterize and describe both species, validating the rat as a good animal model for human pathologies. We also present the comparative analysis of dorsal and ventral DG isolated from the rats.

Development of Lipitor

From Sankyo’s experience, Roger Newton and his pharmacology colleagues at Parke-Davis learned that the rat is not a good animal model for cholesterol-lowering drugs because the rat’s liver is able to rapidly compensate for the drop of cholesterol. So, for initial in vivo efficacy studies, Newton’s team chose guinea pigs and divided them into two sets: one normal group and the other a chow-fed group. The pharmacologists then gave different groups of guinea pigs Merck’s Mevacor (lovastatin) as a reference or CI-981 in one of three different doses. When the results were tabulated, Parke-Davis scientists were underwhelmed: not only was CI-981 no better than lovastatin in lowering cholesterol, but it seemed even a little inferior. However, they continued with the animal studies with a higher species—the dog. They used cholestyramine-primed dogs since the plasma cholesterol-lowering effects became more pronounced after the dogs had been fed with the cholesterol-lowering resin. Unfortunately, again in dogs, CI-981 showed LDL-cholesterol–lowering efficacy about the same as that of lovastatin at the doses tested. Upon further scrutiny of the data, the only advantage that the pharmacologists could fi nd was that CI-981 lowered triglyceride levels slightly better (20–40%) than lovastatin in those animal models. In 1988, Mevacor had already been on the market for an entire year. Merck’s Zocor and Bristol-Myers Squibb’s Pravachol were poised to be launched in 1991, and Sandoz’s Lescol would be ready to launch in 1994. In addition, Rhône- Poulenc Rorer’s dalvastatin was at a similar stage as CI-981 in development. Either dalvastatin or CI-981 would have become the fifth of its kind on the market. Parke-Davis believed that they would need differentiation in order to successfully sell its drug. After all, CI-981 had to be different from, hopefully better than, existing drugs, for them to make a good profit. Parke-Davis’s belief that they needed to differentiate CI-981 from existing statins had its root in another Parke-Davis drug, Accupril (quinapril), an ACE inhibitor poised to launch in 1991.

Depth from shading and disparity in humans and monkeys

A stimulus display was devised that enabled us to examine how effectively monkeys and humans can process shading and disparity cues for depth perception. The display allowed us to present these cues separately, in concert and in conflict with each other. An oddities discrimination task was used. Humans as well as monkeys were able to utilize both shading and disparity cues but shading cues were more effectively processed by humans. Humans and monkeys performed better and faster when the two cues were presented conjointly rather than singly. Performance was significantly degraded when the two cues were presented in conflict with each other suggesting that these cues are processed interactively at higher levels in the visual system. The fact that monkeys can effectively utilize depth information derived from shading and disparity indicates that they are a good animal model for the study of the neural mechanisms that underlie the processing of these two depth cues.

Risk Factors for Infant Abuse and Neglect in Group-Living Rhesus Monkeys

This study investigated maternal abuse and neglect of offspring in a large population of rhesus monkeys over a period of 29 years. Abuse and neglect did not occur together and were associated with different risk factors. Infant abuse was concentrated in 8 of 57 families and among closely related females. Abuse was also repeated with successive offspring. In contrast, infant neglect was not affected by genealogical factors, was not repeated with successive offspring, and was displayed mostly by primiparous mothers. These results suggest that abuse and neglect may be different phenomena and that infant abuse in group-living monkeys could represent a good animal model for investigating the mechanisms underlying the intergenerational transmission of child maltreatment.

Haemoperfusion treatment in pigs experimentally intoxicated by paraquat

1 Because of their similarity in renal morphology and physiology to humans, domestic pigs (gilts, 70 kg) were bolus treated by intramuscular injection of 74,17, and 6 mg kg-1 and by oral loading (70 mg kg-1 n=4) of paraquat. The concentration peak of plasma paraquat was reached at 1.5 - 2.5 h. Renal clearance of paraquat rose to its maximum at 5 - 6 h after intoxication and then sharply decreased indicating renal failure. All the intoxicated pigs died. 2 An additional 10 gilts were also orally treated with 70 mg kg-1 paraquat but received haemoperfusion from 2 h post intoxication for either 2 h (n=6) or 6 h (n=4). The 2 h haemoperfusion resulted in a 5.1% toxin removal but failed to save any of six poisoned pigs. Prolonged 6 h haemoperfusion successfully rescued three out of four intoxicated pigs. 3 The plasma paraquat concentrations of the three surviving pigs were above 2 mg l -1 at 10 h post intoxication. This level is not only similar to those of untreated animals that died later, but also well beyond the suggested limit for survival of poisoned patients. 4 Pigs proved to be a good animal model for studies in paraquat poisoning and/or haemoperfusion. It is also suggested that early haemoperfusion is effective in treating paraquat poisoning even in very severe cases due to its possible detoxicating effect in addition to toxin removal.

Interactions of sperm and the reproductive ducts of the male tammar wallaby, Macropus eugenii (Macropodidae: Marsupialia)

This review compares sperm production in the tammar wallaby and eutherian mammals, particularly the rat. The capacity of sperm to fertilize an ovum when they leave the testis and the changes they undergo in the epididymidis are considered. The structural differentiation and regulation of the extratesticular duct system is assessed and related to the reabsorption and secretion of water, inorganic ions and proteins, and the interaction of sperm and proteins synthesized and secreted by the epididymidis. Adaptations of the cauda epididymidis for storing spermatozoa are also considered. It is suggested that the tammar may be a good animal model to study the suppression of sperm motility and metabolism in the cauda epididymidis as it is possible to collect from them luminal samples of sperm which are initially immotile and then spontaneously activate during incubation in vitro.

Circadian rhythm of glycogen in the hamster diaphragm

The purpose of this study was to determine the diurnal fluctuation of glycogen stores for the whole hemidiaphragm and within a specific myofibrillar ATPase (M-ATPase) fibre type and diaphragmatic region. Fifty-six golden Syrian hamsters were randomly divided into six groups according to the time of sampling biopsies from the diaphragm: 03:00, 07:00, 11:00, 15:00, 19:00, and 23:00. The right hemidiaphragm was quick frozen and biochemically assayed for glycogen levels. Biopsies from the left hemidiaphragm of the same animal were cut from the anterior costal and crural regions, and stained with periodic acid – Schiff (PAS) and for M-ATPase. Optical density measures of PAS-stained fibres were determined to quantitate glycogen in different M-ATPase fibre types and diaphragmatic regions. Biochemical assay of the entire hemidiaphragm showed slightly greater glycogen content of biopsies taken at 11:00 and 15:00 than at 03:00, 19:00, and 23.00 (range of differences: 6.4–10.0%). However, glycogen levels within a specific M-ATPase fibre type and diaphragm region were not different in biopsies sampled at different times. Because the hamster has a small diurnal variation of glycogen in the diaphragm, which is similar to the small diurnal variation of glycogen in human skeletal muscle, this species may be a good animal model for metabolic studies of the diaphragm that could be affected by diurnal glycogen variability.Key words: periodic acid – Schiff, costal region, crural region, fibre type.