Neuroscience
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The corticospinal tract is widely used to study regeneration and is essential for voluntary movements in humans. In young rats, corticospinal axons on the uninjured side sprout and grow into the denervated side. Neurotrophin-3 (NT-3) induces such crossed collateral sprouting in adults. ⋯ NT-3 caused sprouting of local calcitonin gene-related peptide-positive fibers. These results suggest that NT-3 reduces collateral sprouting of spared corticospinal axons from within the denervated regions, possibly because of the injury environment or by increasing sprouting of local afferents. They identify an unexpected context-dependent outgrowth inhibitory effect of NT-3.
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Transgenic mice ectopically expressing nerve growth factor in oligodendrocytes have high levels of nerve growth factor immunoreactivity in the white matter of the spinal cord from birth until 2 months of age. The nerve growth factor over-expression leads to the appearance of ectopic substance P containing sensory fibers in the white matter of the spinal cord that persist throughout the life of the animal. These transgenic mice have been found to display hypersensitivity to a thermal stimulus following a sensitizing pinch stimulus known to release endogenous substance P. ⋯ Furthermore, we detected immunoreactivity for the mu-opioid receptor in the ectopic fibers, where it was co-localized with endomorphin-2 immunoreactivity. In the superficial dorsal horn, there were no apparent differences in the distribution and intensity of mu-opioid receptor immunoreactivity between wild type and transgenic animals. Taken together, these data could provide an explanation for the enhanced effect of opioid analgesics in transgenic mice, when compared with control mice, as well as provide the basis for studies of the postnatal development of the hyperalgesia and allodynia demonstrated by these animals.
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Comparative Study
Activation of lateral hypothalamic neurons stimulates brown adipose tissue thermogenesis.
The lateral hypothalamic area, containing orexin neurons, is involved in several aspects of autonomic regulation, including thermoregulation and energy expenditure. To determine if activation of lateral hypothalamic area neurons influences sympathetically-regulated thermogenesis in brown adipose tissue, we microinjected bicuculline (120 pmol, 60 nl, unilateral) into the lateral hypothalamic area in urethane/chloralose-anesthetized, artificially-ventilated rats. ⋯ Subsequent microinjections of glycine (30 nmol, 60 nl) to inhibit local neurons in raphe pallidus or in dorsomedial hypothalamus or of glutamate receptor antagonists into dorsomedial hypothalamus promptly reversed the increases in brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature and heart rate evoked by disinhibition of neurons in lateral hypothalamic area. We conclude that neurons in the lateral hypothalamic area can influence brown adipose tissue sympathetic nerve activity, brown adipose tissue thermogenesis and heart rate through pathways that are dependent on the activation of neurons in dorsomedial hypothalamus and raphe pallidus.
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Comparative Study
Increase in proliferation and gliogenesis but decrease of early neurogenesis in the rat forebrain shortly after transient global ischemia.
Regarding regenerative strategies early post-ischemic therapeutic interventions might have a great impact on further pathophysiological cascades. To understand the early post-ischemic events we analyzed proliferation and neurogenesis as early as on day 3 after transient global ischemia in rats. Evaluations were performed not only in the dorsal hippocampus, where post-ischemic cell death develops selectively in the cornu ammonis, subfield 1 area, but also in distant areas like the ventricle wall and the striatum. ⋯ Interestingly, in locally defined zones we found nestin- and glial fibrillary acidic protein-signals clearly separated. In sham-operated animals, nestin could be detected in both neurogenic zones only without co-labeling with glial markers. In conclusion, during the first days after global ischemia, cell death of cornu ammonis, subfield 1-neurons was accompanied by a massive overall proliferation and activation of microglia/macrophages, a reduction of pre-ischemia existing doublecortin-positive precursors in the dentate gyrus and a re-expression of nestin in glial fibrillary acidic protein-positive astrocytes.
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Environmental synchronization of the endogenous mammalian circadian rhythm involves glutamatergic and GABAergic neurotransmission within the hypothalamic suprachiasmatic nucleus (SCN). The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits light-induced phase shifts, evokes K(+)-currents and reduces the intracellular Ca(2+) concentration in SCN neurons. Since these effects are consistent with a modulatory role for N/OFQ on synaptic transmission in the SCN, we examined the effects of N/OFQ on evoked and spontaneous excitatory and inhibitory currents in the SCN. ⋯ However, N/OFQ had no effect on currents activated by muscimol application or on the amplitude of miniature IPSC (mIPSC) and significantly reduced the mIPSC frequency consistent with an inhibition of GABA release downstream from Ca(2+) entry. Finally, N/OFQ inhibited the paired-pulse depression observed in SCN GABAergic synapses consistent with a presynaptic mechanism of action. Together these results suggest a widespread modulatory role for N/OFQ on the synaptic transmission in the SCN.