Cognitive performance of healthy young rats following chronic donepezil administration.

RATIONALE: Experimental studies have investigated the effects of chronic donepezil treatment on the behavioral deficits elicited by reduced activity or the loss of cholinergic neurons that occurs in aging or in models of dementia. However, few studies have analyzed the effects of chronic donepezil treatment on the cognitive functions of intact animals. OBJECTIVES: The cognitive functions of healthy young rats treated chronically with the acetylcholinesterase inhibitor donepezil were evaluated using a wide behavioral test battery. RESULTS: Chronic treatment with donepezil ameliorated memory functions and explorative strategies, speeded up the acquisition of localizing knowledge, augmented responsiveness to the context, and reduced anxiety levels. However, it did not affect spatial span, modify motivational levels, or influence associative learning. CONCLUSIONS: The present findings show the specific profile of donepezil action on cognitive functions in the presence of unaltered cholinergic neurotransmission systems

Cerebellar involvement in cognitive flexibility

The aim of the present study was to investigate whether the cerebellar structures are involved in functions requiring cognitive flexibility abilities. The flexibility of the hemicerebellectomized and control animals in learning a four-choice learning task, adapting to ever-changing response rules was investigated. While in the initial phase of the task both experimental groups exhibited similar performances, only the control animals significantly improved their performance as the sessions went by. The lack of improvement in lesioned animals' performance rendered their responses particularly defective in the final phases of the task, when conversely intact animals performed best, exploiting their "learning to learn" ability. The findings demonstrate the defective influence of the cerebellar lesion on the acquisition, not the execution, of new responses. The results underline the crucial role of the cerebellum in mediating cognitive flexibility behaviors

IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Historically, senescence has been considered a safe program in response to multiple stresses in which cells undergo irreversible growth arrest. This process is characterized by morphological and metabolic changes, heterochromatin formation, and secretion of inflammatory components, known as senescence-associated secretory phenotype (SASP). However, recent reports demonstrated that anti-cancer therapy itself can stimulate a senescence response in tumor cells, the so-called therapy-induced senescence (TIS), which may represent a temporary bypass pathway that promotes drug resistance. In this context, several studies have shown that EGFR blockage, by TKIs or moAbs, promotes TIS by increasing IL-1 cytokine production, thus pushing cells into a "pseudo-senescent" state. Today, senotherapeutic agents are emerging as a potential strategy in cancer treatment thanks to their dual role in annihilating senescent cells and simultaneously preventing their awakening into a resistant and aggressive form. Here, we summarize classic and recent findings about the cellular processes driving senescence and SASP, and we provide a state-of-the-art of the anti-cancer strategies available so far that exploits the activation and/or blockade of senescence-based mechanisms

New Early Eocene mammalian fauna from western Patagonia, Argentina

Two new fossil mammal localities from the Paleogene of central-western Patagonia are preliminarily described as the basis for a new possible biochronological unit for the early Eocene of Patagonia, correlated as being between two conventional SALMAs, the Riochican (older) and the Vacan subage of the Casamayoran SALMA. The mammal-bearing strata belong to the Middle Chubut River Volcanic-Pyroclastic Complex (northwestern Chubut Province, Argentina), of Paleocene-Eocene age. This complex includes a variety of volcaniclastic, intrusive, pyroclastic, and extrusive rocks deposited after the K-T boundary. Geochronological data taken from nearby volcanic deposits that underlie and overlie the mammal-bearing levels indicate that both faunas are of late early Eocene age (Ypresian-Lutetian boundary). In addition to more than 50 species of mammals, including marsupials, ungulates, and xenarthrans, two lower molars are the oldest evidence of bats in South America. Paleobotanical and palynological evidence from inferred contemporary localities nearby indicate subtropical environments characterized by warm and probably moderately humid climate. Remarkably, this new fauna is tentatively correlated with Eocene mammals from the La Meseta Formation in the Antarctic Peninsula. We conclude that the two localities mentioned above are part of a possible new biochronological unit, but the formal proposal of a new SALMA awaits completion of taxonomic analysis of the materials reported upon here. If the La Meseta fauna is correlated biochronologically to western Patagonia, this also suggests a continental extension of the biogeographic Weddelian Province as far north as central-western Patagonia

Short-Term Enrichment Makes Male Rats More Attractive, More Defensive and Alters Hypothalamic Neurons

Innate behaviors are shaped by contingencies built during evolutionary history. On the other hand, environmental stimuli play a significant role in shaping behavior. In particular, a short period of environmental enrichment can enhance cognitive behavior, modify effects of stress on learned behaviors and induce brain plasticity. It is unclear if modulation by environment can extend to innate behaviors which are preserved by intense selection pressure. In the present report we investigate this issue by studying effects of relatively short (14-days) environmental enrichment on two prominent innate behaviors in rats, avoidance of predator odors and ability of males to attract mates. We show that enrichment has strong effects on both the innate behaviors: a) enriched males were more avoidant of a predator odor than non-enriched controls, and had a greater rise in corticosterone levels in response to the odor; and b) had higher testosterone levels and were more attractive to females. Additionally, we demonstrate decrease in dendritic length of neurons of ventrolateral nucleus of hypothalamus, important for reproductive mate-choice and increase in the same in dorsomedial nucleus, important for defensive behavior. Thus, behavioral and hormonal observations provide evidence that a short period of environmental manipulation can alter innate behaviors, providing a good example of gene-environment interaction

Biochronological relationships of South American Paleogene mammalian faunas.

International audienc

Biochronological relationships of South American Paleogene mammalian faunas.

International audienc

BDNF concentrations are decreased in serum and parietal cortex in immunotoxin 192 IgG-Saporin rat model of cholinergic degeneration.

The neurotrophin brain-derived neurotrophic factor (BDNF) has been extensively studied because of its role in survival, differentiation and function of neurons undergoing degeneration in pathological conditions such as cholinergic neurons in Alzheimer's disease (AD). However, despite these evidences, the role of BDNF in these events is still matter of debate because central and peripheral BDNF levels are often found in opposite direction. Another puzzling factor is represented by pharmacological treatments known to cause alterations of BDNF peripheral levels. Thus, a pivotal issue would be to verify whether brain and serum BDNF changes are interconnected as well as the possibility that different stages of cholinergic degeneration are characterized by different changes in BDNF brain and serum levels. With this in mind in this study we used a rat model of cholinergic degeneration based on intracerebro-ventricular (icy.) injections of 192 IgG-Saporin and measured brain and serum BDNF concentrations by enzyme-linked immunosorbent assay (ELISA) at 3,7 and 15 days from immunotoxin injection. We found that BDNF levels were reduced in parietal cortex and serum of Saporin-treated rats at 15 days from lesion. Moreover, a positive correlation between serum and parietal cortex was observed at 15 days from lesion. These alterations were not present at the earlier post-operative time points. In conclusion, this study shows that BDNF levels are reduced in a rat model of cholinergic degeneration and suggests that these alterations may occur at later stages. In addition, a positive correlation between serum and parietal cortex changes is observed. Even if the cause for the relationship between BDNF in serum and this brain region is unknown, these data may help to elucidate the significance of peripheral and central BDNF changes in brain pathological conditions. (C) 2011 Elsevier B.V. All rights reserved