65 research outputs found
The Intrinsic Role of Epigenetics in Axonal Regeneration
No full textAxonal injury causes devastating neural impairment, which is often permanent after central nervous system (CNS) damage. Axon regeneration failure is largely responsible for these long-term deficits and poor functional recovery, and is attributable to cell-intrinsic mechanisms and to the nonpermissive cell-extrinsic environment, which together limit axon regrowth
The plasticity of plasticity: lesson from remote microglia induced by focal central nervous system injury.
No full textno abstrac
The "Janus-faced role" of autophagy in neuronal sickness: focus on neurodegeneration.
No full textThe mature brain is a highly dynamic organ that constantly changes its organization by destroying and forming new connections. Collectively, these changes are referred to as brain plasticity and are associated with functional changes, such as memory, addiction, and recovery of function after brain damage. Neuronal plasticity is sustained by the fine regulation of protein synthesis and organelle biogenesis and their degradation to ensure efficient turnover. Thus, autophagy, as quality control mechanism of proteins and organelles in neurons, is essential to their physiology and pathology. Here, we review recent several findings proving that defects in autophagy affect neuronal function and impair functional recovery after brain insults, contributing to neurodegeneration, in chronic and acute neurological disorders. Thus, an understanding of the molecular mechanisms by which the autophagy machinery is finely regulated might accelerate the development of therapeutic interventions in many neurological disorders for which no cure is available
Hemicerebellectomy
No full textHemicerebellectomy (HCB) is characterized by ablation of half of the vermis with one cerebellar hemisphere, including the deep cerebellar nuclei, while sparing the vestibular nuclei and all surrounding structures. This approach has been adopted widely by many groups mainly in rats in various contexts of research. The purpose of this chapter is to review old and recent data focusing on morphological as well as functional data obtained in this model in addressing cerebellar function and brain plasticity mechanisms
Remote neurodegeneration: multiple actors for one play.
No full textRemote neurodegeneration significantly influences the clinical outcome in many central nervous system (CNS) pathologies, such as stroke, multiple sclerosis, and traumatic brain and spinal cord injuries. Because these processes develop days or months after injury, they are accompanied by a therapeutic window of opportunity. The complexity and clinical significance of remote damage is prompting many groups to examine the factors of remote degeneration. This research is providing insights into key unanswered questions, opening new avenues for innovative neuroprotective therapies. In this review, we evaluate data from various remote degeneration models to describe the complexity of the systems that are involved and the importance of their interactions in reducing damage and promoting recovery after brain lesions. Specifically, we recapitulate the current data on remote neuronal degeneration, focusing on molecular and cellular events, as studied in stroke and brain and spinal cord injury models. Remote damage is a multifactorial phenomenon in which many components become active in specific time frames. Days, weeks, or months after injury onset, the interplay between key effectors differentially affects neuronal survival and functional outcomes. In particular, we discuss apoptosis, inflammation, oxidative damage, and autophagy-all of which mediate remote degeneration at specific times. We also review current findings on the pharmacological manipulation of remote degeneration mechanisms in reducing damage and sustaining outcomes. These novel treatments differ from those that have been proposed to limit primary lesion site damage, representing new perspectives on neuroprotection
Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research
No full textEarly life stres
Nilotinib: from animal-based studies to clinical investigation in Alzheimer's disease patients
No full textSince their first description in the brains of patients suffering from Alzheimer’s disease (AD), more than 100 years ago, extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles have been the principal focus of AD research. However, this focus has led to the failure of several long and promising clinical trials, and the efficacy of new Aβ-targeting drugs to slow down the disease progression is still controversial despite being successful in reducing the Aβ load.
Thus, despite the discouraging results, the lessons that have been learned from the Aβ debacle have prompted studies focusing on new molecular targets that regulate different cellular pathways and have formulated new hypotheses for investigating the involvement of different brain regions beyond the temporal lobe, including the hippocampal region
Early life stress-induced neuroinflammation and neurological disorders: A novel perspective for research
No full textNON
Strain-dependent variations in stress coping behavior are mediated by a 5-HT/GABA interaction within the prefrontal corticolimbic system.
No full textSerotonin and γ-aminobutyric acid (GABA) transmission is crucial in coping strategies.
METHODS:
Here, using mice from 2 inbred strains widely exploited in behavioral neurochemistry, we investigated whether serotonin transmission in medial prefrontal cortex and GABA in basolateral amygdala determine strain-dependent liability to stress response and differences in coping.
RESULTS:
C57BL/6J mice displayed greater immobility in the forced swimming test, higher serotonin outflow in medial prefrontal cortex, higher GABA outflow in basolateral amygdala induced by stress, and higher serotonin 1A receptor levels in medial prefrontal cortex accompanied by lower GABAb receptor levels in basolateral amygdala than DBA/2J mice. In assessing whether serotonin in medial prefrontal cortex determines GABA functioning in response to stress and passive coping behavior in C57BL/6J and DBA/2J mice, we observed that selective prefrontal serotonin depletion in C57BL/6J and DBA/2J reduced stress-induced GABA outflow in basolateral amygdala and immobility in the forced swimming test.
CONCLUSIONS:
These results show that strain-dependent prefrontal corticolimbic serotonin/GABA regulation determines the strain differences in stress-coping behavior in the forced swimming test and point to a role of a specific neuronal system in genetic susceptibility to stress that opens up new prospects for innovative therapies for stress disorders
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