Neuroscience
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Cholinergic neurons of the pontine laterodorsal tegmentum (LDT) play a critical role in regulation of behavioral state. Therefore, elucidation of mechanisms that control their activity is vital for understanding of how switching between wakefulness, sleep and anesthetic states is effectuated. In vivo studies suggest that GABAergic mechanisms within the pons play a critical role in behavioral state switching. ⋯ All of these GABA-mediated actions were found to occur in histochemically-identified cholinergic neurons. Taken together, these data indicate for the first time that cholinergic neurons of the LDT exhibit functional GABA(A, B and C) receptors, including extrasynaptically located GABA(A) receptors, which may be tonically activated by synaptic overflow of GABA. Accordingly, the activity of cholinergic LDT neurons is likely to be significantly affected by GABAergic tone within the nucleus, and so, demonstrated effects of GABA on behavioral state may be mediated, in part, via direct actions on cholinergic neurons in the LDT.
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Oxidative stress and inflammation are important processes in the progression of Alzheimer's disease (AD). Recent studies have implicated the role of amyloid β-peptides (Aβ) in mediating these processes. In astrocytes, oligomeric Aβ induces the assembly of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complexes resulting in its activation to produce anionic superoxide. ⋯ Our data showed that laser light at 632.8 nm suppressed Aβ-induced superoxide production, colocalization between NADPH oxidase gp91(phox) and p47(phox) subunits, phosphorylation of cPLA(2,) and the expressions of IL-1β and iNOS in primary astrocytes. We demonstrated for the first time that 632.8 nm laser was capable of suppressing cellular pathways of oxidative stress and inflammatory responses critical in the pathogenesis in AD. This study should prove to provide the groundwork for further investigations for the potential use of laser therapy as a treatment for AD.
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We examined whether repeated exposure to the increasingly abused amphetamine (AMPH) derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) results in long-lasting neurobehavioral changes, and further, the ability of contextual cues to modulate these changes. We focused on dorsal striatum, a brain region implicated in the formation of persistent drug-related habits. Rats were transported to a novel recording chamber and treated with once-daily injections (s.c.) of (±)-MDMA (5.0 mg/kg) or saline for 5 days, followed by a challenge injection 14 days later either in the same (Experiment 1) or different context (Experiment 2). ⋯ Furthermore, several alterations in striatal electrophysiology were apparent on challenge day, but only in rats that displayed sensitization. Conversely, structural changes in striatal medium spiny neurons, such as increases in spine density, were observed in MDMA-treated rats regardless of whether they displayed behavioral sensitization. Thus, it appears that reorganization of synaptic connectivity in dorsal striatum may contribute to long-lasting drug-induced behavioral alterations, but that these behavioral alterations are subject to modification depending on individual differences and the context surrounding drug administration.
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Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (n=9) or mixed with citalopram 5 mg/kg/day (n=27). ⋯ As was observed with citalopram, fluoxetine induced significant reductions of TPH cell counts in the DRN (39%), MRN (38%) and RMN (41%), with no significant differences in the CLN. These results indicate that SERT inhibition can alter the regulation of TPH, the rate limiting enzyme for serotonin biosynthesis. This persistent and regionally specific downregulation of serotonin biosynthesis may account for some of the clinical withdrawal symptoms associated with drugs that inhibit SERT.
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The hippocampus plays a central role in memory formation in the mammalian brain. The subiculum is the principal target of CA1 pyramidal cells and thus serves as the major relay station for the outgoing hippocampal information. Pyramidal cells in the subiculum have been classified as burst-spiking (BS) and regular-spiking (RS) cells. ⋯ The isoproterenol-induced LTP in (BS) cells does not depend on postsynaptic Ca(2+)-signaling, as 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) does not prevent its induction. Furthermore, paired-pulse facilitation (PPF) and coefficient of variation (CV) analysis indicate the site of the LTP expression to be presynaptic. Our findings show that activation of β-adrenergic receptors (β-ARs) at CA1-subiculum synapses induces a cell-type-specific form of chemical LTP in subicular (BS) cells that may allow a target-specific trafficking of hippocampal output.