Neuroscience
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Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. ⋯ The estrous cycle neither impacted behavior nor TRP metabolite levels in the FSL rat. In conclusion, the female FSL rat is an interesting preclinical model of depression with altered TRP metabolism, independent of the estrous cycle. The status of the pathway in brain was not reflected in the plasma, which may indicate that an inherent local, cerebral regulation of TRP metabolism occurs.
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Autophagy plays an essential role in neurodevelopment, axonal guidance, neuropathic pain remission, and neuronal survival. Inhibiting the mammalian target of rapamycin (mTOR) signaling pathway can induce the occurrence of autophagy. In this study, we initially detected the effect of probucol on autophagy after spinal cord injury (SCI) by intraperitoneally injecting spinal cord-injured rats with probucol for 7days. ⋯ Immunofluorescence results indicated that the expression of Caspase-3 protein was evidently decreased and that of Beclin-1 protein was increased by probucol. Nissl staining and Basso, Beattie, and Bresnahan scores showed that the quantity and function of motor neurons were visibly preserved by probucol after SCI. This study showed that probucol inhibited the mTOR signaling pathway to induce autophagy, reduce neural cell apoptosis and promote recovery of neurological function after SCI.
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The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I-III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty in identifying glutamatergic synapses with light microscopy. ⋯ We also examined several populations of glutamatergic axons and found that most boutons were in contact with at least one Homer punctum. These results suggest that Homer antibodies can be used to reveal the great majority of glutamatergic synapses without antigen retrieval. This will be of considerable value in tracing synaptic circuits, and also in investigating plasticity of glutamatergic synapses in pain states.
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Huntington's disease (HD) is characterized by progressive motor symptoms preceded by cognitive deficits and is regarded as a disorder that primarily affects the basal ganglia. The external globus pallidus (GPe) has a central role in the basal ganglia, projects directly to the cortex, and is majorly modulated by GABA. To gain a better understanding of the time course of HD progression and gain insight into the underlying mechanisms, we analyzed GABAergic neurotransmission in the GPe of the R6/1 mouse model at purportedly asymptomatic and symptomatic stages (i.e., 2 and 6months). ⋯ Actigraphy analyses revealed rest/activity fragmentation alterations that parallel GABAergic system impairment at 2months, while the locomotor deficit is evident only at 3months in R6/1 mice. Our results reveal early deficits in HD and support growing evidence for a critical role played by the GPe in physiological and pathophysiological states. We suggest that actimetry may be used as a non-invasive tool to monitor early disease progression.
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Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl-d-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. ⋯ None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors.