Caveolin-1 and altered neuregulin signaling contribute to the pathophysiological progression of diabetic peripheral neuropathy.

OBJECTIVE: Evaluate if Erb B2 activation and the loss of caveolin-1 (Cav1) contribute to the pathophysiological progression of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Cav1 knockout and wild-type C57BL/6 mice were rendered diabetic with streptozotocin, and changes in motor nerve conduction velocity (MNCV), mechanical and thermal hypoalgesia, Erb B2 phosphorylation (pErb B2), and epidermal nerve fiber density were assessed. The contribution of Erb B2 to DPN was assessed using the Erb B2 inhibitors PKI 166 and erlotinib and a conditional bitransgenic mouse that expressed a constitutively active form of Erb B2 in myelinated Schwann cells (SCs). RESULTS: Diabetic mice exhibited decreased MNCV and mechanical and thermal sensitivity, but the extent of these deficits was more severe in diabetic Cav1 knockout mice. Diabetes increased pErb B2 levels in both genotypes, but the absence of Cav1 correlated with a greater increase in pErb B2. Erb B2 activation contributed to the mechanical hypoalgesia and MNCV deficits in both diabetic genotypes because treatment with erlotinib or PKI 166 improved these indexes of DPN. Similarly, induction of a constitutively active Erb B2 in myelinated SCs was sufficient to decrease MNCV and induce a mechanical hypoalgesia in the absence of diabetes. CONCLUSIONS: Increased Erb B2 activity contributes to specific indexes of DPN, and Cav1 may be an endogenous regulator of Erb B2 signaling. Altered Erb B2 signaling is a novel mechanism that contributes to SC dysfunction in diabetes, and inhibiting Erb B2 may ameliorate deficits of tactile sensitivity in DPN.

Phylogeny of finescale shiners of the genus Lythrurus (Cypriniformes: Cyprinidae) inferred from four mitochondrial genes.

We infer the phylogenetic relationships of finescale shiners of the genus Lythrurus, a group of 11 species of freshwater minnows widely distributed in eastern North America, using DNA sequences from the ND2 (1047 bp), ATPase8 and 6 (823 bp), and ND3 (421 bp) mitochondrial protein-coding genes. The topologies resulting from maximum parsimony, Bayesian, and maximum likelihood tree building methods are broadly congruent, with two distinct clades within the genus: the L. umbratilis clade (L. umbratilis + L. lirus + (L. fasciolaris + (L. ardens, L. matutinus))) and the L. bellus clade (L. fumeus + L. snelsoni + (L. roseipinnis + (L. atrapiculus + (L. bellus, L. algenotus)))). Support is weak at the base of several clades, but strongly supported nodes differ significantly from prior investigations. In particular, our results confirm and extend earlier studies recovering two clades within Lythrurus corresponding to groups with largely "northern" and "southern" geographic distributions. Several species in this genus are listed in the United States as threatened or of special concern due to habitat degradation or limited geographic ranges. In this study, populations assigned to L. roseipinnis show significant genetic divergence suggesting that there is greater genetic diversity within this species than its current taxonomy reflects. A full accounting of the biodiversity of the genus awaits further study.