Neuroscience
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The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. ⋯ We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity.
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Many clinical studies have reported on the benefits of exercise therapy in patients with Parkinson's disease (PD). Exercise cannot stop the progression of PD or facilitate the recovery of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) (Bega et al., 2014). To tease apart this paradox, we utilized a progressive MPTP (1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine) mouse model in which we initiated 4weeks of treadmill exercise after the completion of toxin administration (i.e., restoration). ⋯ There was an increase in GLT-1 levels in the striatum due to exercise, with no change in striatal BDNF protein expression. Our data suggest that motor recovery was not prompted by any significant restoration of DA neurons or terminals, but rather the recovery of DAT and dampening the inflammatory response. Although exercise does not promote recovery of nigrostriatal DA, it should be used in conjunction with pharmaceutical methods for controlling PD symptoms.
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12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia-induced memory impairment and cholinergic deficits. ⋯ The inhibition of 12/15 LOX resulted in a significant decrease in NO levels in the hippocampal homogenate associated with downregulated iNOS, nNOS transcription but not eNOS speculating that 12/15 LOX is critically involved in HIF-1α, mediated by nitric oxide-induced neurotoxicity. We also observed a similar effect of 12/15 LOX inhibition on hippocampal COX2 expression. 12/15LOX inhibition could effectively modulate central cholinergic indices during hypobaric hypoxia by restoring mAChR-1, α7NAChR expression and AChE, ChAT activity in the hippocampus comparable to normal mice. We report here the mechanistic involvement of 12/15LOX in orchestrating hypoxia-associated neuronal damage and HIF-1α-dependent neuroinflammation resulting in cognitive decline.
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Activation of the serotonin type 4 (5-HT4) receptors has been reported to improve abdominal pain in patients with functional gastrointestinal disorders and reduce visceral nociception in animal models. Earlier studies have proposed that 5-HT4 agonist can produce visceral analgesia by acting at the supraspinal level, but the underlying neuronal mechanisms remain unclear. The caudal ventrolateral medulla (CVLM) is the first site for processing of visceral nociceptive signals ascending via spinal pathways and an important component of the endogenous pain modulatory system. ⋯ The compound's inhibitory effect was almost completely eliminated by intracerebroventricular pretreatment with GR113808, a selective 5-HT4 antagonist, indicating the preferential involvement of supraspinal 5-HT4 receptors. Results indicate that visceral nociceptive transmission through the caudal medulla is negatively modulated by descending 5-HT4-dependent mechanisms. These findings can contribute to a deeper understanding of supraspinal processing of pain signals from the abdomen.
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Many neuropsychiatric disorders show localized dysfunction in specific cortical regions. The mechanisms underlying such region-specific vulnerabilities are unknown. Post-mortem analyses have demonstrated a selective reduction in the expression of parvalbumin (PV) in GABAergic interneurons in the frontal rather than the sensory cortex of patients with neuropsychiatric disorders such as schizophrenia, autism spectrum disorders, and bipolar disorders. ⋯ Our results show that the regions frequently affected in neuropsychiatric disorders show significantly lower PV expression and a lower percentage of PV neurons surrounded by PNNs in the brains of socially isolated mice. These results indicate that PV neurons and PNNs exhibit region-specific vulnerabilities. Our findings may be useful for elucidating the mechanisms underlying region-specific disruption of the brain in neuropsychiatric disorders.