Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring.

A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation.

Heme Oxygenase-1 and Brain Oxysterols Metabolism Are Linked to Egr-1 Expression in Aged Mice Cortex, but Not in Hippocampus.

Throughout life, stress stimuli act upon the brain leading to morphological and functional changes in advanced age, when it is likely to develop neurodegenerative disorders. There is an increasing need to unveil the molecular mechanisms underlying aging, in a world where populations are getting older. Egr-1 (early growth response 1), a transcriptional factor involved in cell survival, proliferation and differentiation - with a role also in memory, cognition and synaptic plasticity, can be implicated in the molecular mechanism of the aging process.

Downregulation of canonical Wnt signaling in hippocampus of SAMP8 mice.

In the adult brain, canonical Wnt (Wnt/β-catenin) signaling modulates neuronal function, hippocampal neurogenesis, and synaptic plasticity. Indeed, growing evidence suggests that downregulation of Wnt signaling could be involved in the cognitive decline associated with aging and also with the physiopathology of Alzheimer's disease (AD). However, the molecular basis remains unknown.

Mavoglurant as a treatment for Parkinson's disease.

Introduction: A major unresolved issue in the Parkinson's disease (PD) treatment is the development of l-DOPA-induced dyskinesias (LIDs) as a side effect of chronic L-DOPA administration. Currently, LIDs are managed in part by reducing the L-DOPA dose or by the administration of amantadine. However, this treatment is only partially effective.

Antiapoptotic drugs: a therapautic strategy for the prevention of neurodegenerative diseases.

The purpose of this review is to discuss potential pathways involved in the pathogenesis of neurodegenerative diseases, highlighting current pharmacological drug targets in neuronal apoptosis prevention. The incidence of these disorders is expected to rise in the coming years and so finding effective treatments represents a significant challenge for medicine. Alzheimer's disease and Parkinson's disease were both described almost a century ago and are the most important neurodegenerative disorders in the developed world.

Enhanced tau phosphorylation in the hippocampus of mice treated with 3,4-methylenedioxymethamphetamine ("Ecstasy").

3,4-Methylenedioxymethamphetamine (MDMA) ("Ecstasy") produces neurotoxic effects, which result into an impairment of learning and memory and other neurological dysfunctions. We examined whether MDMA induces increases in tau protein phosphorylation, which are typically associated with Alzheimer's disease and other chronic neurodegenerative disorders. We injected mice with MDMA at cumulative doses of 10-50 mg/kg intraperitoneally, which are approximately equivalent to doses generally consumed by humans.

Inhibition of ataxia telangiectasia-p53-E2F-1 pathway in neurons as a target for the prevention of neuronal apoptosis.

Over the last few decades, understanding of the mechanisms involved in the process of neuronal cell death has grown. Recent findings have established that DNA damage, and specifically ataxia telangiectasia mutated protein (ATM), is key to the cascade of regulation of neuronal apoptosis. Another characteristic common to all neurodegenerative diseases is oxidative stress.

Increased permeability of blood-brain barrier on the hippocampus of a murine model of senescence.

SAMP8 mice show several indicative characteristics of accelerated aging and have been used to study the physiological and physiopathological processes that take place during senescence. There is some controversy about the presence of a functional blood-brain barrier (BBB) disturbance on these animals, which could be related to the oxidative stress or the amyloidosis present in their brain. In order to elucidate BBB status in the hippocampus of SAMP8 mice, in this study we have determined the extravasation from brain microvessels of endogenous IgG in SAMP8 mice aged 3, 7 and 12 months and in age-matched control SAMR1 mice.

The role of CDK5/P25 formation/inhibition in neurodegeneration.

Cdk5 is an atypical cyclin-dependent kinase localized in the brain, and its activity is dependent upon binding to p35/p39. In addition, while cdk5 has important physiological functions related to brain development, the breakdown of cdk5/p35 into cdk5/p25 increases its kinase activity and neurotoxicity. Interestingly, in recent years increased cdk5/p25 expression has been demonstrated in the brains of patients with Alzheimer's and Parkinson's diseases.

Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8.

The senescence-accelerated strains of mice (SAMP) are well-characterized animal models of senescence. Senescence may be related to enhanced production or defective control of reactive oxygen species, which lead to neuronal damage. Therefore, the activity of various oxidative-stress related enzymes was determined in the cortex of 5 months-old senescence-accelerated mice prone-8 (SAMP-8) of both sexes and compared with senescence-accelerated mice-resistant-1 (SAMR-1).

Inhibition of multiple pathways accounts for the antiapoptotic effects of flavopiridol on potassium withdrawal-induced apoptosis in neurons.

Serum and potassium (S/K) deprivation is a well-known apoptotic model in cerebellar granule neurons (CGNs), used to study the efficacy of potential neuroprotective drugs. The objective of this study was to determine the pathways involved in the neuroprotective role of flavopiridol, a pan-inhibitor of cyclin-dependent kinases (CDKs), upon S/K withdrawal-induced apoptosis in CGNs. Cell death in primary cultures of rat CGNs was accompanied by chromatin condensation and activation of caspases-3, -6, and -9.

p21(WAF1/Cip1) is not involved in kainic acid-induced apoptosis in murine cerebellar granule cells.

Kainic acid (KA) treatment induced neuronal death and apoptosis in murine cerebellar granule cells (CGNs) cultures from both wild-type and knockout p21(-/-) mice. There was not statistically significant difference in the percentage of neuronal apoptosis among strains. KA-induced neurotoxicity was prevented in the presence of NBQX (20 microM) and GYKI 52446 (20 microM), but not by z-VAD-fmk, suggesting that caspases are not involved in the apoptotic process.

Cyclosporin A enhances colchicine-induced apoptosis in rat cerebellar granule neurons.

1. Cyclosporin A (CsA, 1-50 microM), an immunosuppressive drug with known neurotoxic effects, did not decrease the viability of primary cultures of rat cerebellar granule neurons (CGN) or induce apoptotic features. However, CsA specifically enhanced the cytotoxicity and apoptosis induced by colchicine (1 microM).