Neuroscience
-
In the present study, we characterized differential expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase IIalpha (pCaMKIIalpha) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1 beta) significantly increased pCaMKIIalpha expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-alpha, and IL-1beta but not by s.c. injections of formalin or i.p. injections of acetic acid. ⋯ PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERKalpha and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKIIalpha in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner.
-
The protein fragment nesfatin-1 was recently implicated in the control of food intake. Central administration of this fragment results in anorexia and reduced body weight gain, whereas antisense or immunological nesfatin-1 antagonism causes increased food intake and overweight. Nesfatin-1 is derived from the precursor nucleobindin-2 (NUCB2). ⋯ Furthermore, nesfatin was extensively colocalized with cocaine- and amphetamine-regulated transcript in almost all NUCB2-expressing brain regions. These data reveal a wider distribution of NUCB2/nesfatin-1 than previously known, suggesting that the metabolic actions of this protein may involve not only feeding behavior but also endocrine and autonomic effects on energy expenditure. In addition, the subcellular distribution of nesfatin-like immunoreactivity indicates that this protein may not be processed like a conventional secreted neuromodulator.
-
To understand plastic changes in the dorsal horn related to neuropathic pain, we developed a model of decompression in rats with chronic constriction injury (CCI) and investigated corresponding changes in the dorsal horn. At postoperative week 4 (POW 4) of CCI, rats were divided into a decompression group, in which ligatures were removed, and a CCI group, in which ligatures remained. Spinal cords were immunostained for substance P (SP), the delta-opioid receptor (DOR), and calcitonin gene-related peptide (CGRP). ⋯ In the CCI group, neuropathic pain behaviors became normalized at POW 12 with corresponding changes in dorsal horn indexes for both SP and DOR similar to those of the decompression group. In contrast, changes in the dorsal horn indexes of CGRP were similar in both the CCI and decompression groups throughout the experimental period. These findings suggest that CCI and decompression cause different patterns in peptidergic and DOR (+) nerve terminals in the dorsal horn.
-
Among the GABAergic neocortical interneurons, fast-spiking (FS) basket and chandelier cells are essential mediators for feed-forward inhibition, network synchrony and oscillations. The FS properties are in part mediated by the voltage-gated potassium channels Kv3.1b/3.2 which allow the fast repolarization of the membrane necessary for firing non-adapting action potentials at high frequencies. It has been recently reported that the FS phenotype fails to mature in BDNF knockout mice suggesting a role for neurotrophins. ⋯ Only NT4 increased the expression of both mRNAs later in development. Kv3 protein levels were not changed by exogenous tropomyosin-related kinase B (TrkB) ligands, but the levels decreased upon inhibiting the MAPK signaling suggesting a role for endogenous factors and in particular MEK2 signaling for translation. The results show that Kv3.1b/3.2 expression is differentially controlled by neuronal activity and neurotrophic factors.
-
Strabismus in human infants is linked strongly to nasotemporal asymmetries of smooth pursuit, but many features of this co-morbidity are unknown. The purpose of this study was to determine how the duration of early-onset strabismus (or timeliness of repair) affects the severity of pursuit asymmetries in a primate model. ⋯ Binocular decorrelation in primates during an early period of fusion development causes permanent smooth pursuit asymmetries when the duration exceeds the equivalent of 3 months in human. These findings support the conclusion that early correction of infantile strabismus promotes normal development of cerebral gaze pathways.