Neuroscience
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A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR). ⋯ In addition, LFP and multiunit activity within the visually responsive superficial layers of the SC showed the SHR to have a hyper-responsive SC relative to control strains, which could not be explained by altered functioning of the retinocollicular pathway. Finally, examination of collicular volume, neuron and glia densities and glia:neuron ratio revealed that the SHR had a reduced ratio relative to the WKY which could explain the increased responsiveness. In conclusion, this study demonstrates strain-specific changes in the functioning and structure of the SC in the SHR, providing convergent evidence that the SC might be dysfunctional in ADHD.
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Sustained administration of cannabinoid agonists acting on neuronal CB1 receptors (CB1Rs) are proposed for treating spasticity and chronic pain. The impact of CB1Rs on mammalian locomotor networks remains, however, incompletely understood. To clarify how CB1Rs may control synaptic activity and locomotor network function, we used the rat spinal cord in vitro which is an advantageous model to investigate locomotor circuit mechanisms produced by the local central pattern generator. ⋯ Since CB1R activation usually inhibits cyclic adenosine monophosphate (cAMP) synthesis, we investigated how a 24-h application of AEA or AM-251 affected basal or forskolin-stimulated cAMP levels. While AEA decreased them in an AM-251-sensitive manner, AM-251 per se did not change resting or stimulated cAMP. Our data suggest that CB1Rs may control the circuit gateway regulating the inflow of sensory afferent inputs into the locomotor circuits, indicating a potential site of action for restricting peripheral signals disruptive for locomotor activity.
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Our previous studies have suggested that surgical lesions of the rat cochlea induce cell proliferation in the cochlear nucleus (CN) that may be related to neurogenesis. The aim of the present study was to further investigate the nature of cell proliferation in the CN, following acoustic trauma that has previously been shown to induce tinnitus in rats. Rats were subjected either to a unilateral acoustic trauma (16-kHz pure tone, 115dB for 1h under anesthesia) or a sham procedure. ⋯ Immunolabeling revealed the BrdU(+ve) cells to co-express Ki-67 and DCX, but not CD-11b. However, there was no difference in DCX expression between sham and exposed animals. The results suggest that DCX-expressing cells in the CN may proliferate in response to acoustic trauma; however, the proportion of cells proliferating and the survival rate of the newborn cells may not support functional neurogenesis in the CN.
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Epilepsy and seizure activity result in the generation of reactive oxygen species (ROS), which contribute to seizure-induced neuronal damage. Recent in vitro evidence indicates that NADPH oxidase contributes significantly to seizure-induced ROS. We further tested this in rat glio-neuronal cultures and in ex vivo chronic epileptic rat brain tissue using live cell-imaging techniques. ⋯ Inhibition of ROS production by AEBSF, a NADPH oxidase inhibitor, markedly reduced seizure-induced cell death in the perforant path model of epilepsy. These findings demonstrate a critical role for ROS, generated by NADPH oxidase, contributing to seizure-induced cell death. These findings point to NADPH oxidase inhibition as a novel treatment strategy to prevent brain injury in SE and chronic epilepsy.
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Hypertension is the most significant modifiable risk factor for vascular cognitive impairment. However, influence of hypertension on the development of ischemic white matter injury and cognitive dysfunction is not fully understood. We compared cognitive functions and neuropathological outcomes of chronic cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAO) between normotensive rats (NRs) and spontaneously hypertensive rats (SHRs). ⋯ Although no significant changes in the gross structure of myelinated white matter or oligodendrocyte number were noted, BCCAO resulted in subtle myelin degeneration and paranodal structural alterations at the nodes of Ranvier, regardless of hypertension. Disruption of the blood-brain barrier (BBB) was predominantly observed in the white matter of SHRs following BCCAO, implying a role of hypertension in BBB dysfunction in chronic cerebral hypoperfusion. In chronic cerebral ischemia, long-standing hypertension may aggravate impairment of BBB integrity, and the leaky BBB may in turn exacerbate dysfunction in the white matter leading to worsening of spatial cognitive performance.