“Skittish” Abca2 Knockout Mice Display Tremor, Hyperactivity, and Abnormal Myelin Ultrastructure in the Central Nervous System

ABSTRACT The ATP-binding cassette transporter 2 (ABCA2) is an endolysosomal protein most highly expressed in the central and peripheral nervous system tissues and macrophages. Previous studies indicated its role in cholesterol/steroid (estramustine, estradiol, and progesterone) trafficking/sequestration, oxidative stress response, and Alzheimer's disease. Developmental studies have shown its expression during macrophage and oligodendrocyte differentiation, processes requiring membrane growth. To determine the in vivo function(s) of this transporter, we generated a knockout mouse from a gene-targeted disruption of the murine ABCA2 gene. Knockout males and females are viable and fertile. However, a non-Mendelian inheritance pattern was shown among male progeny of heterozygous crosses. Compared to wild-type and heterozygous littermates, knockout mice displayed a tremor without ataxia, hyperactivity, and reduced body weight; the latter two phenotypes were more marked in females than in males. This sexual disparity suggests a role for ABCA2 in hormone-dependent neurological and/or developmental pathways. Myelin sheath thickness in the spinal cords of knockout mice was greatly increased compared to that in wild-type mice, while a significant reduction in myelin membrane periodicity (compaction) was observed in both spinal cords and cerebra of knockout mice. Loss of ABCA2 function in vivo resulted in abnormal myelin compaction in spinal cord and cerebrum, an ultrastructural defect that we propose to be the cause of the phenotypic tremor.

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Immune Response in the Absence of Neurovirulence in Mice Infected with M Protein Mutant Vesicular Stomatitis Virus

Journal of Virology ◽

10.1128/jvi.00915-08 ◽

2008 ◽

Vol 82 (18) ◽

pp. 9273-9277 ◽

Cited By ~ 30

Author(s):

Maryam Ahmed ◽

Tracie R. Marino ◽

Shelby Puckett ◽

Nancy D. Kock ◽

Douglas S. Lyles

Keyword(s):

Central Nervous System ◽

Immune Response ◽

Nervous System ◽

Vesicular Stomatitis Virus ◽

M Protein ◽

Wild Type ◽

Protein Mutants ◽

The Central Nervous System ◽

Vesicular Stomatitis

ABSTRACT Matrix (M) protein mutants of vesicular stomatitis virus (VSV), such as rM51R-M virus, are less virulent than wild-type (wt) VSV strains due to their inability to suppress innate immunity. Studies presented here show that when inoculated intranasally into mice, rM51R-M virus was cleared from nasal mucosa by day 2 postinfection and was attenuated for spread to the central nervous system, in contrast to wt VSV, thus accounting for its reduced virulence. However, it stimulated an antibody response similar to that in mice infected with the wt virus, indicating that it has the ability to induce adaptive immunity in vivo without causing disease. These results support the use of M protein mutants of VSV as vaccine vectors.

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Role of endothelin-1 in stress response in the central nervous system

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.2.r515 ◽

2000 ◽

Vol 279 (2) ◽

pp. R515-R521 ◽

Cited By ~ 16

Author(s):

Yukiko Kurihara ◽

Hiroki Kurihara ◽

Hiroyuki Morita ◽

Wei-Hua Cao ◽

Guang-Yi Ling ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Stress Responses ◽

Knockout Mice ◽

Biological Activities ◽

Close Association ◽

Immunohistochemical Analysis ◽

Catecholamine Metabolism ◽

Wild Type ◽

The Central Nervous System

Endothelin (ET)-1 is a 21-amino acid peptide that induces a variety of biological activities, including vasoconstriction and cell proliferation, and its likely involvement in cardiovascular and other diseases has recently led to broad clinical trials of ET receptor antagonists. ET-1 is widely distributed in the central nervous system (CNS), where it is thought to regulate hormone and neurotransmitter release. Here we show that CNS responses to emotional and physical stressors are differentially affected in heterozygous ET-1-knockout mice, which exhibited diminished aggressive and autonomic responses toward intruders (emotional stressors) but responded to restraint-induced (physical) stress more intensely than wild-type mice. This suggests differing roles of ET-1 in the central pathways mediating responses to different types of stress. Hypothalamic levels of ET-1 and the catecholamine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were both increased in wild-type mice subjected to intruder stress, whereas MHPG levels were not significantly affected in ET-1-knockout mice. Furthermore, immunohistochemical analysis showed that ET-1 and tyrosine hydroxylase, an enzyme in the catecholamine synthesis pathway, were colocalized within certain neurons of the hypothalamus and amygdala. Our findings suggest that ET-1 modulates central coordination of stress responses in close association with catecholamine metabolism.

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Coordinated Regulation and Widespread Cellular Expression of Interferon-Stimulated Genes (ISG) ISG-49, ISG-54, and ISG-56 in the Central Nervous System after Infection with Distinct Viruses

Journal of Virology ◽

10.1128/jvi.01167-06 ◽

2006 ◽

Vol 81 (2) ◽

pp. 860-871 ◽

Cited By ~ 95

Author(s):

Christie Wacher ◽

Marcus Müller ◽

Markus J. Hofer ◽

Daniel R. Getts ◽

Regina Zabaras ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Dominant Role ◽

Lymphocytic Choriomeningitis ◽

Wild Type ◽

Cellular Expression ◽

The Central Nervous System ◽

The Brain ◽

Lcmv Infection

ABSTRACT The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions.

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Faculty Opinions recommendation of Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108807.567147 ◽

2008 ◽

Author(s):

Murali Ramanathan

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Myeloid Cells ◽

The Central Nervous System

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Faculty Opinions recommendation of Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108807.565335 ◽

2008 ◽

Author(s):

Reinhard Hohlfeld

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Myeloid Cells ◽

The Central Nervous System

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Faculty Opinions recommendation of Real-time in vivo imaging of fungal migration to the central nervous system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717957672.793462077 ◽

2012 ◽

Author(s):

Stéphane Bretagne ◽

Alexandre Alanio

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Real Time ◽

In Vivo Imaging ◽

The Central Nervous System

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Plant Species of Sub-Family Valerianaceae—A Review on Its Effect on the Central Nervous System

Plants ◽

10.3390/plants10050846 ◽

2021 ◽

Vol 10 (5) ◽

pp. 846

Author(s):

Gitishree Das ◽

Han-Seung Shin ◽

Rosa Tundis ◽

Sandra Gonçalves ◽

Ourlad Alzeus G. Tantengco ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Plant Species ◽

Current Knowledge ◽

Biological Properties ◽

In Vivo Studies ◽

Food Species ◽

The Central Nervous System ◽

Preclinical And Clinical Studies

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

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A radiotracer method for the measurement of central nervous system catecholamines in vivo

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y78-085 ◽

1978 ◽

Vol 56 (3) ◽

pp. 535-538 ◽

Cited By ~ 6

Author(s):

S. W. Tang ◽

H. C. Stancer ◽

J. J. Warsh

Keyword(s):

Central Nervous System ◽

Animal Model ◽

Nervous System ◽

Specific Activity ◽

Brain Catecholamines ◽

Radiotracer Method ◽

New Strategy ◽

The Central Nervous System ◽

6 Hydroxydopamine

A new strategy for measurement of brain catecholamines was tested in an animal model. [3H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.

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