The European journal of neuroscience
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Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. ⋯ The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'.
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Chondroitin sulphate proteoglycans (CSPGs) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC (ChABC). Here we assess whether CSPG degradation can promote compensatory sprouting of the intact corticospinal tract (CST) following unilateral injury and restore function to the denervated forelimb. Adult C57BL/6 mice underwent unilateral pyramidotomy and treatment with either ChABC or a vehicle control. ⋯ Immunohistochemical assessment of chondroitin-4-sulphate revealed that CSPGs were heavily digested around lamina X, alongside midline crossing axons and in grey matter regions where sprouting axons and reduced peri-neuronal net staining was observed. Thus, we demonstrate that CSPG degradation promotes midline crossing and reinnervation of denervated target regions by intact CST axons and leads to restored function in the denervated forepaw. Enhancing compensatory sprouting using ChABC provides a route to restore function that could be applied to disorders such as spinal cord injury and stroke.
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Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. ⋯ HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits.
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The dorsal raphe nucleus (DRN) and ventrolateral periaqueductal grey (vlPAG) regions contain populations of dopamine neurons, often considered to be a dorsal caudal extension of the A10 group [mostly found in the ventral tegmental area (VTA)]. Recent studies suggest they are involved in promoting wakefulness and mediate some of the antinociceptive and rewarding properties of opiates. However, little is known about their electrophysiological properties. ⋯ They fire broad action potentials at a relatively slow, regular rate, exhibit a hyperpolarization-activated inward current and delayed repolarization, and show spike-frequency adaptation in response to prolonged depolarization. In addition, they receive fast excitatory and inhibitory synaptic inputs. Moreover, we found co-expression of vasoactive intestinal polypeptide in small, periaqueductal dopamine neurons, but generally not in larger, more ventral dopamine neurons.
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Neuropathic pain (NP) often presents with comorbidities, including depression and anxiety. The amygdala is involved in the processing of mood disorders, fear, and the emotional-affective components of pain. Hemispheric lateralization of pain processing in the amygdala has recently been brought to light because, independently of the side of the peripheral injury, the right central nucleus of the amygdala (CeA) showed higher neuronal activity than the left in models of inflammatory pain. ⋯ Overall, we observed that peripheral nerve injury produced asymmetric plasticity in ongoing and evoked activity in the left and right CeA. Remarkably, at 14 days after SNL induction, enhanced evoked activity in the right CeA persisted compared to short-term increases in activity in the left CeA. The plasticity found in ongoing and evoked activity was inhibited by pregabalin.