Neuroscience
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The mammillary body (MB) and the anterior thalamic nuclei (ATN) are closely related structures, which take part in learning and memory processes. However, the exact role of these structures has remained unclear. In both structures neurons firing according to hippocampal theta rhythm have been found, mainly in the medial mammillary nucleus (MM) and anteroventral thalamic nucleus (AV). ⋯ The inactivation of the MM resulted in decrease in EEG power in the HP and AV, the most evidently in the lower theta frequency bands, i.e. 3-5Hz in the HP (down to 9.2% in 3- to 4-Hz band and 37.6% in 4- to 5-Hz band, in comparison to the power in the control conditions) and 3-4Hz in the AV (down to 24.9%). After the AV inactivation, hippocampal EEG power decreased in theta frequency bands of 3-8Hz (down to 61.6% in 6- to 7-Hz band and 69.4% in 7- to 8-Hz band). Our results suggest that the role of the MB-ATN axis in regulating theta rhythm signaling may be much more important than has been speculated so far.
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Alzheimer's disease (AD) is the most prevalent disorder of senile dementia mainly characterized by amyloid-beta peptide (Aβ) deposits in the brain. Cannabinoids are relevant to AD as they exert several beneficial effects in many models of this disease. Still, whether the endocannabinoid system is either up- or down-regulated in AD has not yet been fully elucidated. ⋯ Conversely, a high availability of 2-AG resulting from an increase in DAGL and lysophosphatidic acid phosphohydrolase activities occurred in the presence of Aβ1-40 fibrils although synaptosomal membrane disruption was also observed. Interestingly, neither synaptosomal mitochondrial viability assayed by MTT reduction nor membrane lipid peroxidation assayed by TBARS formation measurements were altered by Aβ1-40 oligomers or fibrils. These results show a differential effect of Aβ1-40 peptide on 2-AG metabolism depending on its conformation.
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The basal forebrain cholinergic pathways progressively degenerate during the progression of Alzheimer's disease, leading to an irreversible impairment of memory and thinking skills. The stereotaxic lesion with 192IgG-saporin in the rat brain has been used to eliminate basal forebrain cholinergic neurons and is aimed at emulating the cognitive damage described in this disease in order to explore its effects on behavior and on neurotransmission. Learning and memory processes that are controlled by cholinergic neurotransmission are also modulated by the endocannabinoid (eCB) system. ⋯ The decrease in CB1 receptor density observed in the hippocampus, together with hyperactivity of eCB signaling in the NBM and cortex, suggest an interaction between the eCB and cholinergic systems. Moreover, following basal forebrain cholinergic denervation, the presynaptic GABAergic immunoreactivity was reduced in cortical areas. In conclusion, CB1 receptors present in presynaptic GABAergic terminals in the hippocampus are down regulated, but not those in cortical glutamatergic synapses.
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Amyloid-β (Aβ) production and clearance in the brain is a crucial focus of investigations into the pathogenesis of Alzheimer disease. Imbalance between production and clearance leads to accumulation of Aβ. The important Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), and defective enzyme expression may facilitate Aβ deposition in sporadic late-onset AD patients. ⋯ NEP expression in cultured astrocytes was suppressed by activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), and reduced NEP expression was accompanied by an increase of NEP release into the extracellular space (culture medium). Moreover, culture medium from EGCG-treated astrocytes facilitated the degradation of exogenous Aβ. These results suggest that EGCG may have a beneficial effect on AD by activating ERK-and PI3K-mediated pathways in astrocytes, thus increasing astrocyte secretion of NEP and facilitating degradation of Aβ.
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Oligodendrocyte progenitor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during early stages of post-natal life. However, OPCs persist beyond developmental myelination and represent an important population of cycling cells in the gray and white matter of the adult brain. While adult OPCs form unique territories that are maintained through self-avoidance, some cortical OPCs appear to position their cell body very close to that of a neuron, forming what are known as OPC-neuron pairs. ⋯ Density of OPC-neuron pairs was increased by the GABAA receptor antagonist picrotoxin. Finally, histological analysis of OPC-neuron pairs suggested that in the dorsal portion of the cortex, GABAergic interneurons represent the most common neuronal component of the pairs, and that calbindin, calretinin and parvalbumin GABAergic interneurons found in the cortex take part in these pairs. Using previous estimates of the number of GABAergic neurons in the rodent cortex, we estimate that roughly one in four GABAergic neurons are paired with an OPC.