Neuroscience
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Basal forebrain cholinergic neurons (BFCN) are selectively vulnerable to damage and loss in a number of neurodegenerative disorders that afflict the elderly, particularly Alzheimer's disease. The reasons for this selective vulnerability remain poorly understood. Given that intraneuronal accumulation of the amyloid-β peptide (Aβ) has been shown to exert deleterious effects on neurons, we tested potential accumulation of Aβ within BFCN in rhesus monkeys, which like the human display age-related accumulation of this peptide in plaques. ⋯ In some nbM-Ch4 neurons, 1282 immunoreactivity had the appearance of large peptide aggregates. Significant accumulation and age-related increase of Aβ in BFCN is likely to interfere with the normal functioning of these neurons. It remains to be determined if similar accumulation of Aβ occurs in human BFCN.
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Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. ⋯ In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy.
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Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. ⋯ Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.
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Aging is accompanied by a complicated pattern of changes in the brain organization and often by alterations in specific memory functions. One of the brain activities with important role in the process of memory consolidation is thought to be the hippocampus activity of sharp waves and ripple oscillation (SWRs). Using field recordings from the CA1 area of hippocampal slices we compared SWRs as well as single pyramidal cell activity between adult (3-6-month old) and old (24-34-month old) Wistar rats. ⋯ CPP increased the postsynaptic excitability and the paired-pulse inhibition in slices from both adult and old rats similarly while nifedipine increased the postsynaptic excitability only in slices from adult rats. We propose that the tendency of the aged hippocampus to generate long sequences of SWR events might represent the consequence of homeostatic mechanisms that adaptively try to compensate the impairment in the ripple oscillation in order to maintain the behavioral outcome efficient in the old individuals. The age-dependent alterations in the firing mode of pyramidal cells might underlie to some extent the changes in ripples that occur in old animals.
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Located in the nerve terminals of serotonergic neurons, 5-HT1B autoreceptors are poised to modulate synaptic 5-HT levels with precise temporal and spatial control, and play an important role in various emotional behaviors. This study characterized two novel, complementary viral vector strategies to investigate the contribution of 5-HT1B autoreceptors to fear expression, displayed as freezing, during contextual fear conditioning. ⋯ Surprisingly, selective expression of 5-HT1B autoreceptors in just this circuit led to an increase in fear expression in WT, but not 1BKO, mice. These results suggest that activation of 5-HT1B autoreceptors throughout the brain may have an overall effect of attenuating fear expression, but activation of subsets of 5-HT1B autoreceptors in particular brain regions, reflecting distinct projections of serotonergic neurons from the DRN, may have disparate contributions to the ultimate response.