Neuroscience
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The analgesic effect of opioids decreases over time due to the development of analgesic tolerance. We have shown that inhibition of the platelet-derived growth factor beta (PDGFR-β) signaling eliminates morphine analgesic tolerance in rats. Although the PDGFR-β and its ligand, the platelet-derived growth factor type B (PDGF-B), are expressed in the substantia gelatinosa of the spinal cord (SG) and in the dorsal root ganglia (DRG), their precise distribution within different cell types of these structures is unknown. ⋯ Consistent with our previous finding that morphine caused tolerance by inducing PDGF-B release, PDGF-B was upregulated in the spinal cord. We also found that chronic morphine exposure caused a spinal proliferation of oligodendrocytes. The changes in PDGFR-β and PDGF-B expression induced by chronic morphine treatment suggest potential mechanistic substrates underlying opioid tolerance.
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Iron supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. ⋯ Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.
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Tauopathies are a group of neurodegenerative diseases among which are many of the most prevalent and with higher incidence worldwide, such as Alzheimer's disease (AD). According to the World Health Organization, this set of diseases will continue to increase their incidence, affecting millions of people by 2050. All of them are characterized by aberrant aggregation of tau protein in neurons and glia that are distributed in different brain regions according to their susceptibility. ⋯ Despite this, it has not been emphasized how the glial inclusions of tau in this cell type directly affect this and many other essential functions, whose alterations have been related to the development of tauopathies. In this way, this review shows how tau inclusions in glia influence the synaptic dysfunctions that result in the cognitive symptoms characteristic of tauopathies. Thus, the mechanisms affected by inclusions in neurons, astrocytes, and oligodendrocytes are unraveled.
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Tau is a well-known microtubule-associated protein related to its cytoplasmic localization in a neuronal cell. However, tau has been located at the cell nucleus where it could be a nucleic acid-associated protein by its preferential binding to DNA sequences present in the nucleolus and pericentromeric heterochromatin. This less well-known localization of tau could not be trivial, since during aging, an increase in the amount of nuclear tau takes place and it may be related to the described role of tau in the activation of transposons and further aging acceleration.
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Gut microbiota represents a diverse and dynamic population of microorganisms harbouring the gastrointestinal tract, which influences host health and disease. Bacterial colonization of the gastrointestinal tract begins at birth and changes throughout life, with age being one of the conditioning factors for its vitality. Aging is also a primary risk factor for most neurodegenerative diseases. ⋯ Data from clinical studies as well as the link between microbiome and clinical determinants of AD are particularly emphasized. Further, relationships between gut microbiota and age-dependent epigenetic changes and other neurological disorders are also described. Together, all this evidence suggests that, in some sense, gut microbiota can be seen as an additional hallmark of human aging and neurodegeneration.