Lingual and palatal gustatory afferents each depend on both BDNF and NT‐4, but the dependence is greater for lingual than palatal afferents

Neurons of the geniculate ganglion innervate taste buds located in two spatially distinct targets, the tongue and palate. About 50% of these neurons die in Bdnf^−/− mice and Ntf4/5^−/− mice. Bdnf^−/−/Ntf4/5^−/− double mutants lose 90–95% of geniculate ganglion neurons. To determine whether different subpopulations are differentially influenced by neurotrophins, we quantified neurons from two ganglion subpopulations separately and remaining taste buds at birth within each target field in wild‐type, Bdnf^−/−, Ntf4/5^−/−, and Bdnf^−/−/Ntf4/5^−/− mice. In wild‐type mice the same number of neurons innervated the anterior tongue and soft palate and each target contained the same number of taste buds. Compared to wild‐type mice, Bdnf^−/− mice showed a 50% reduction in geniculate neurons innervating the tongue and a 28% loss in neurons innervating the soft palate. Ntf4/5^−/− mice lost 58% of the neurons innervating the tongue and 41% of the neurons innervating the soft palate. Taste bud loss was not as profound in the NT‐4 null mice compared to BDNF‐null mice. Tongues of Bdnf^−/−/Ntf4/5^−/− mice were innervated by 0 to 4 gustatory neurons and contained 3 to 16 taste buds at birth, indicating that some taste buds remain even when all innervation is lost. Thus, gustatory neurons are equally dependent on BDNF and NT‐4 expression for survival, regardless of what peripheral target they innervate. However, taste buds are more sensitive to BDNF than NT‐4 removal. J. Comp. Neurol. 518:3290–3301, 2010. © 2010 Wiley‐Liss, Inc.     

Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes

Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212-2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c-Fos expression and by an overexpression of mu-opioid and cannabinoid CB1 and CB2 receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin-nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A-fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain.     

Molecular cloning and expression of a GABA receptor subunit from the crayfish Procambarus clarkii

Molecular cloning has introduced an unexpected, large diversity of neurotransmitter hetero‐ oligomeric receptors. Extensive research on the molecular structure of the γ‐aminobutyric acid receptor (GABAR) has been of great significance for understanding how the nervous system works in both vertebrates and invertebrates. However, only two examples of functional homo‐oligomeric GABA‐activated Cl^? channels have been reported. In the vertebrate retina, the GABAρ1 subunit of various species forms homo‐oligomeric receptors; in invertebrates, a cDNA encoding a functional GABA‐activated Cl^? channel has been isolated from a Drosophila melanogaster head cDNA library. When expressed in Xenopus laevis oocytes, these subunits function efficiently as a homo‐oligomeric complex. To investigate the structure–function of GABA channels from the crayfish Procambarus clarkii, we cloned a subunit and expressed it in human embryonic kidney cells. Electrophysiological recordings show that this subunit forms a homo‐oligomeric ionotropic GABAR that gates a bicuculline‐insensitive Cl^? current. The order of potency of the agonists was GABA > trans‐4‐amino‐crotonic acid = cis‐4‐aminocrotonic acid > muscimol. These data support the notion that X‐organ sinus gland neurons express at least two GABA subunits responsible for the formation of hetero‐oligomeric and homo‐oligomeric receptors. In addition, by in situ hybridization studies we demonstrate that most X‐organ neurons from crayfish eyestalk express the isolated pcGABA_Aβ subunit. This study increases the knowledge of the genetics of the crayfish, furthers the understanding of this important neurotransmitter receptor family, and provides insight into the evolution of these genes among vertebrates and invertebrates. © 2015 Wiley Periodicals, Inc.     

State-dependent increase in the levels of neurotrophin-3 and neurotrophin-4/5 in patients with bipolar disorder: A meta-analysis

Bipolar disorder (BD) is one of the most serious psychiatric disorders in the world, but its pathophysiology is still unclear. Regulation of neurotrophic factors have been thought to play a role in this process. There have been inconsistent findings regarding the differences in blood neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) between patients with BD and healthy controls (HCs). The aim of the current meta-analysis is to examine the changes in the levels of NT-3 and NT-4/5 in BD patients at different affective states. Eight articles (including 465 BD patients and 353 HCs) were included in the analysis, and their results were pooled by using a random effects model. We found the levels of both NT-3 (p = 0.0046) and NT-4/5 (p = 0.0003) were significantly increased in BD patients, compared to HCs. Through subgroup analysis, this increase persisted only in patients in depressed state (p = 0.0038 for NT-3 and p = 0.0001 for NT-4/5), but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. Our results suggest a state-dependent increase in NT-3 and NT-4/5 levels in patients with BD. Further studies are needed to examine dynamic changes of these neurotrophins in BD patients along the disease course.