Neuroscience
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Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in the human brain. Although numerous studies in mouse models of Alzheimer disease (AD) have shown a correlation among diet, beta-amyloid and AD onset, little is known about the impact of diet on Tau. We investigated whether a low fat-protein diet (LFPD) may improve lifespan, cognitive and locomotor activity in P301L-tg mouse model of tauopathy. ⋯ For instance, tg females, but not males, fed with LFPD had a significant increase of body weight and a reduction of P-Tau agglomerates compared to tg fed with standard diet. These changes correlated with a more pronounced improvement of cognition and locomotor activity in females than in male tg fed with LFPD. Altogether, these results suggest a sex dependent neuroprotective effect of LFPD in P301L-tg mice, suggesting that lifestyle intervention strategies may be clinically relevant for delaying the onset of cognitive impairment and dementia, especially in females.
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Alzheimer's disease (AD), a debilitating neurodegenerative illness, is characterized by neuronal cell loss, mental deficits, and abnormalities in several neurotransmitter and protein systems. AD is also associated with visual disturbances, but their causes remain unidentified. We hypothesize that the visual disturbances stem from retinal changes, particularly changes in the retinal cholinergic system, and that the etiology in the retina parallels the etiology in the rest of the brain. ⋯ We observed that Tg-SwDI mice showed an initial upregulation of AChR gene expression early on (young adults and middle-aged adults), but a downregulation later on (old adults). Furthermore, transgenic animals displayed significant cell loss in the photoreceptor layer and inner retina of the young adult animals, as well as specific cholinergic cell loss, and increased astrocytic gliosis in the middle-aged adult and old adult groups. Our results suggest that the changes observed in AD cerebrum are also present in the retina and may be, at least in part, responsible for the visual deficits associated with the disease.
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Diabetes mellitus represents a group of metabolic diseases that are characterized by hyperglycemia caused by either lack of insulin production or a reduced ability to respond to insulin. It is estimated that there were 347 million people worldwide who suffered from diabetes in 2008 and incidence is predicted to double by 2050. Neuropathy is the most common complication of long-term diabetes and approximately 30% of these subjects develop chronic neuropathic pain. ⋯ In the current study, we developed chronic and acute insulin-induced neuropathic pain in mice with type 2 insulin-resistant diabetes. Furthermore, we determined that insulin-induced acute allodynia is independent of glycemia levels, can also be induced with Insulin-like Growth Factor 1 (IGF1) and be prevented by inhibition of AKT, providing evidence of an insulin/IGF1 signaling pathway-based mechanism for TIND. This mouse model is useful for the elucidation of mechanisms contributing to TIND and for the testing of new therapeutic approaches to treat TIND.
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The septum is an evolutionarily well-conserved part of the limbic system. It is known to be involved in many aspects of social behavior and is considered a key node of the social behavior network, together with the preoptic area. Involvement of these two brain regions has been recently observed in newly hatched chicks exposed to the natural motion of a living conspecific. ⋯ Here we show that the right septum and the preoptic area of newly hatched visually naïve chicks exposed to speed changes have higher neuronal activity (revealed by c-Fos expression), compared with that of chicks exposed to constant motion. We thus found an involvement of these two areas in the perception of motion cues associated with animacy in newly hatched chicks without any previous visual experience. This demonstrates their early involvement in processing simple motion cues that allow the detection of animate creatures and elicit social predispositions in this animal model, as well as preferential attention in human infants and the perception of animacy in human adults.
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Mutations in the PI3K/Akt/mTOR signaling pathway or in the upstream negative regulator Pten cause human brain overgrowth disorders, such as focal cortical dysplasia and megalencephaly, and are characterized by the presence of hypertrophic neurons. These disorders often have a pediatric onset and a high comorbidity with drug-resistant epilepsy; however, effective pharmacological treatments are lacking. We established forebrain excitatory neuron-specific Pten-deficient cultures as an in vitro model of brain overgrowth disorders, and investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and neuronal growth. ⋯ We found that RAD001 treatment only partially reversed the morphological abnormalities of Pten mutant neurons, whereas MK-2206 treatment completely rescued the phenotype. Interestingly, neither treatment altered the size or morphology of normal neurons. Our results suggest that Akt is a major determinant of neuronal growth, and that Akt inhibition may be an effective strategy for pharmacological intervention in brain overgrowth disorders.