Neuroscience
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Stress plays a pivotal role in the development and/or exacerbation of functional gastrointestinal (GI) disorders. The paraventricular nucleus of the hypothalamus (PVN) contains neurons that are part of the hypothalamic-pituitary-adrenal axis as well as preautonomic neurons innervating, among other areas, gastric-projecting preganglionic neurons of the dorsal vagal complex (DVC). The aim of the present study was to test the hypothesis that stress adaptation upregulates oxytocin (OXT) within PVN-brainstem vagal neurocircuitry. ⋯ Brainstem and hypothalamic nuclei were analyzed immunohistochemically for the presence of both OXT-immunopositive cells in identified preautonomic PVN neurons as well as OXT fibers in the DVC. Rats exposed to chronic homotypic, but not chronic heterotypic stress, had a significant increase in both number of CTB+ OXT co-localized neurons in the PVN as well as density of OXT-positive fibers in the DVC compared to control rats. These data suggest that preautonomic OXT PVN neurons and their projections to the DVC increase following adaptation to stress, and suggest that the possible up-regulation of OXT within PVN-brainstem vagal neurocircuitry may play a role in the adaptation of GI responses to stress.
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Peripheral inflammation often causes changes in mood and emergence of depressive behavior, and is characterized by a group of physical manifestations including lethargy, malaise, listlessness, decreased appetite, anhedonia, and fever. These behavioral changes are induced at the molecular level by pro-inflammatory cytokines like interleukin (IL)-1β, IL-6 and TNF-α. The basolateral amygdala (BLA) is a key brain region involved in mood and may mediate some of the behavioral effects of inflammation. ⋯ Lipopolysaccharide (250 μg/kg, i.p.) increased BLA firing rate acutely (<30 min) and persistently. The findings demonstrate a rapid effect of peripheral inflammation on BLA activity and suggest a link between BLA neuronal firing and triggering of behavioral consequences of peripheral inflammation. These findings are a first step toward understanding the neuronal basis of depressive behavior caused by acute peripheral inflammation.
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Clinical studies have reported lower effectivity of opioid drugs in therapy of neuropathic pain. Therefore, to determine the changes in endogenous opioid systems in this pain more precisely, we have studied the changes in the pain-related behavior on days 1, 14, and 28 following a chronic constriction injury (CCI) to the sciatic nerve in mice. In parallel, we have studied the changes of μ-(MOP), δ-(DOP) and κ-(KOP) receptors, proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels, as well as GTPγS binding of opioid receptors on the ipsi- and contralateral parts of the spinal cord and thalamus on the 14th day following CCI, as on this day the greatest manifestation of pain-related behavior was observed. ⋯ In thalamus, a decrease was observed on the contralateral side for all opioid receptor ligands, especially for DOP ligand. A less pronounced decrease in GTPγS binding of spinal DOP ligands may indicate a weaker stimulation of ascending nociceptive pathways, which could explain the absence of decreased activity of DOP receptor ligands in neuropathy. These findings may suggest that drugs with a higher affinity for the DOP receptor will perform better in neuropathic pain.
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As one of the bisphosphonate derivatives, etidronate has proved to be beneficial to spatial learning and memory deficits caused by two-vessel occlusion (2-VO). In this study, the novel drug etidronate-zinc complex (Eti-Zn) was used to detect its role in synaptic plasticity and learning and memory functions in a rat model of 2-VO. Chronic cerebral hypoperfusion was induced by permanent occlusion of the common carotid artery bilaterally in adult Sprague-Dawley rats. ⋯ Moreover, Eti-Zn treatment reduced both the over-activation of microglia and the expressions of neuroinflammatory cytokines (TNF-α, IL-1β and IL-6) in the hippocampus. The increased NF-κB signaling pathway in the hippocampus of 2-VO rats was reversed after Eti-Zn treatment. In summary, these findings suggest that Eti-Zn could ameliorate the synaptic plasticity and cognitive impairments by reducing neuroinflammation in 2-VO model rats.
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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 8-12% of children globally. Factor analyses have divided ADHD symptoms into two domains: inattention and a combination of hyperactivity and impulsivity. The identification of domain-specific genetic risk variants may help uncover potential genetic mechanisms underlying ADHD. ⋯ We have also found that expression of dopamine-related genes (dopamine transporter, tyrosine hydroxylase, and dopamine D1 and D2 receptors) in the STR increased. Treatment with methylphenidate (5 mg/kg), the most commonly used medication for ADHD, improved attention and normalized expression levels of dopamine-related genes in THRSP OE mice. Our findings suggest that THRSP plays a role in the inattention phenotype of ADHD and that the THRSP OE mice may be used as an animal model to elucidate the genetic mechanisms of the disorder.