Neuroscience
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Peripheral nerve injury induces functional reorganization of the central nervous system. The mechanisms underlying this reorganization have been widely studied. Our previous study involving multiple-site optical recording reported that a neural excitatory wave induced by somatic stimulation begins in a small area and propagates in the cortex. ⋯ Second, changes in the propagation wave pattern were analyzed. Ulnar nerve injury decreased the propagation velocity in the medial direction but the median nerve injury induced no changes. These results indicated that the propagation wave pattern is readily altered, even immediately after nerve injury, and suggest that this immediate change in the spatio-temporal pattern is one of the factors contributing to the cortical reorganization.
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The effects of systemic inflammation on the pathogenesis of Alzheimer's disease (AD) are not clarified, both beneficial and deleterious effects being reported. Allergy is accompanied by a systemic inflammatory response and some epidemiological studies have reported a positive association between a history of allergy/asthma and dementia. To investigate whether chronic airway allergy influences the inflammatory status in the brain, AD-like pathology, and behaviour in relation to AD, we induced chronic airway allergy in triple transgenic AD (3xTgAD) and wildtype (WT) mice by repeated exposure to ovalbumin (OVA) as allergen. ⋯ In contrast, allergy increased the levels of interleukin (IL)-1β and complement component 1q (C1q) in WT mice. Bronchoalveolar lavage fluid analysis confirmed eosinophilia in both genotypes, but the basal levels of eosinophils were lower in 3xTgAD mice. In summary, allergy induced predominantly anti-inflammatory effects in 3xTgAD mice, and pro-inflammatory effects in WT mice, thus being another potential factor to be considered when studying AD pathogenesis.
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The integrity of the perirhinal cortex (PRh) is essential for object recognition memory (ORM) function, and damage to this brain area in animals and humans induces irreversible ORM deficits. Here, we show that activation of area V2, a brain area interconnected with brain circuits of ventral stream and medial temporal lobe that sustain ORM, by expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. ⋯ Thus, RGS14414-mediated activation of area V2 has therapeutic relevance in the recovery of recognition memory, a type of memory that is primarily affected in patients or individuals with symptoms of memory dysfunction. These findings suggest that area V2 modulates the processing of memory-related information through activation of interconnected brain circuits formed by the participation of distinct brain areas.
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Neonatal hypoxic-ischemic encephalopathy is a major cause of mortality and disability in newborns and the only standard approach for treating this condition is therapeutic hypothermia, which shows some limitations. Thus, putative neuroprotective agents have been tested in animal models. The present study evaluated the administration of lactate, a potential energy substrate of the central nervous system (CNS) in an animal model of hypoxia-ischemia (HI), that mimics in neonatal rats the brain damage observed in human newborns. ⋯ Animals underwent behavioral assessments: negative geotaxis, righting reflex (P8 and P14), and cylinder test (P20). Lactate administration reduced the volume of brain lesion and improved behavioral parameters after HI in both sexes. Thus, lactate administration could be a neuroprotective strategy for the treatment of neonatal HI, a disorder still affecting a significant percentage of human newborns.
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Review
POMC Neurons Dysfunction in Diet-induced Metabolic Disease: Hallmark or Mechanism of Disease?
One important lesson from the last decade of studies in the field of systemic energy metabolism is that obesity is first and foremost a brain disease. Hypothalamic neurons dysfunction observed in response to chronic metabolic stress is a key pathogenic node linking consumption of hypercaloric diets with body weight gain and associated metabolic sequelae. ⋯ However, whether such neuronal dysfunction represents a consequence or a mechanism of disease, remains a subject of debate. Here, we will review and highlight emerging pathogenic mechanisms that explain why POMC neurons undergo dysfunctional activity in response to caloric overload, and critically address whether these mechanisms may be causally implicated in the physiopathology of obesity and of its associated co-morbidities.