The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse

<p>Abstract</p> <p>Background</p> <p>Peripherin, a type III neuronal intermediate filament, is widely expressed in neurons of the peripheral nervous system and in selected central nervous system hindbrain areas with projections towards peripheral structures, such as cranial nerves and spinal cord neurons. Peripherin appears to play a role in neurite elongation during development and axonal regeneration, but its exact function is not known. We noticed high peripherin expression in the posterior hypothalamus of mice, and decided to investigate further the exact location of expression and function of peripherin in the mouse posterior hypothalamus.</p> <p>Results</p> <p><it>In situ </it>hybridization indicated expression of peripherin in neurons with a distribution reminiscent of the histaminergic neurons, with little signal in any other part of the forebrain. Immunocytochemical staining for histidine decarboxylase and peripherin revealed extensive colocalization, showing that peripherin is produced by histaminergic neurons in all parts of the tuberomammillary nucleus. We next used histamine immunostaining in peripherin knockout, overexpressing and wild type mice to study if altered peripherin expression affects these neurons, but could not detect any visible difference in the appearance of these neurons or their axons.</p> <p>Peripherin knockout mice and heterozygotic littermates were used for measurement of locomotor activity, feeding, drinking, and energy expenditure. Both genotypes displayed diurnal rhythms with all the parameters higher during the dark period. The respiratory quotient, an indicator of the type of substrate being utilized, also exhibited a significant diurnal rhythm in both genotypes. The diurnal patterns and the average values of all the recorded parameters for 24 h, daytime and night time were not significantly different between the genotypes, however.</p> <p>Conclusion</p> <p>In conclusion, we have shown that peripherin is expressed in the tuberomammillary neurons of the mouse hypothalamus. Monitoring of locomotor activity, feeding, drinking, and energy expenditure in mice either lacking or overexpressing peripherin did not reveal any difference, so the significance of peripherin in these neurons remains to be determined. The complete overlap between histidine decarboxylase and peripherin, both the protein and its mRNA, renders peripherin a useful new marker for histaminergic neurons in the hypothalamus.</p

Transgenic approach to study the role of intermediate filaments in motor neuron disease

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Many reports lead to the hypothesis that a high axonal neurofilament burden and a large axonal caliber account for the selective vulnerability of motor neurons affected in ALS (Kawamura et al., 1981; Sobue et al., 1981; 1987). Transgenic mice expressing a mutant form of SOD1-linked to familial ALS and having one disrupted allele for each neurofilament gene were generated to address this issue. Despite a 40% reduction in neurofilament content and a decrease of large axonal caliber from 5--9 mum to 1--5 mum, these mice did not show an extended life span, nor did they display an alleviated loss of motor axons. These results do not support the idea that high neurofilament content and large axonal caliber are responsible for the selective vulnerability of motor neurons in ALS.Peripherin, a type III intermediate filament (IF) protein is also expressed in spinal motor neurons, and is present together with neurofilaments in axonal spheroids of ALS patients, suggesting that this protein could be involved in the pathogenesis of ALS. Moreover, mice overexpressing a peripherin transgene develop a late-onset motor neuron death characterized by the presence of IF inclusion bodies (Beaulieu et al., 1999a). In a first attempt to clarify the role of peripherin in ALS, peripherin knockout mice were generated. Peripherin null mice were viable, reproduce normally and did not exhibit overt phenotype. However, they did show a 34% reduction in the number of L5 unmyelinated sensory fibers demonstrating a requirement of peripherin for the proper development of a subset of sensory neurons.Finally, in order to investigate whether peripherin contributes to the pathogenesis of ALS, mutant SOD1 mice were generated in a peripherin overexpressing background and a peripherin depleted background. Unexpectedly, upregulation or suppression of peripherin expression had no effect on disease onset, mortality and motor neuron loss in mutant SOD1 mice. Taken together, these results provide compelling evidence that peripherin is not a key contributor of motor neuron degeneration associated with toxicity of mutant SOD1

Sacs R272C missense homozygous mice develop an ataxia phenotype

Abstract Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 200 SACS mutations have been identified. Most mutations lead to a complete loss of a sacsin, a large 520 kD protein, although some missense mutations are associated with low levels of sacsin expression. We previously showed that Sacs knock-out mice demonstrate early-onset ataxic phenotype with neurofilament bundling in many neuronal populations. To determine if the preservation of some mutated sacsin protein resulted in the same cellular and behavioral alterations, we generated mice expressing an R272C missense mutation, a homozygote mutation found in some affected patients. Though Sacs R272C mice express 21% of wild type brain sacsin and sacsin is found in many neurons, they display similar abnormalities to Sacs knock-out mice, including the development of an ataxic phenotype, reduced Purkinje cell firing rates, and somatodendritic neurofilament bundles in Purkinje cells and other neurons. Together our results support that Sacs missense mutation largely lead to loss of sacsin function

The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse-4

Tion of the two proteins in the TM neurons. In A, the ventral/lateral part of the TM nucleus is stained for HDC in red. In B the same area is stained for peripherin (green). The staining for the two proteins is digitally merged in C. Neurons that are stained for both HDC and peripherin appear yellow in this picture. Most neurons are stained for both antigens. Scale bar 20 μm.<p><b>Copyright information:</b></p><p>Taken from "The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse"</p><p>http://www.biomedcentral.com/1471-2202/9/26</p><p>BMC Neuroscience 2008;9():26-26.</p><p>Published online 24 Feb 2008</p><p>PMCID:PMC2266937.</p><p></p

The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse-0

In section hybridized with a S-labelled peripherin probe. The selective staining of the TM nucleus is evident. In B, a digoxigenin labelled mRNA probe reveals the distribution of peripherin expressing neurons in detail. The distribution is very similar to the histaminergic TM neurons. In C, neurons of the lateral TM that were hybridized simultaneously with a digoxigenin labelled probe for peripherin and a S-labelled probe for HDC are shown. The alkaline phosphatase staining for peripherin, which differentiate the neurons from the background, is colocalized with the silver grains that indicate the localization of HDC expression. 3 V, third ventricle. Scale bar 100 μm in B, 20 μm in C.<p><b>Copyright information:</b></p><p>Taken from "The type III neurofilament peripherin is expressed in the tuberomammillary neurons of the mouse"</p><p>http://www.biomedcentral.com/1471-2202/9/26</p><p>BMC Neuroscience 2008;9():26-26.</p><p>Published online 24 Feb 2008</p><p>PMCID:PMC2266937.</p><p></p