Bouts of rest and physical activity in C57BL/6J mice.

The objective was to exploit the raw data output from a scalable home cage (type IIL IVC) monitoring (HCM) system (DVC®), to characterize pattern of undisrupted rest and physical activity (PA) of C57BL/6J mice. The system's tracking algorithm show that mice in isolation spend 67% of the time in bouts of long rest (≥40s). Sixteen percent is physical activity (PA), split between local movements (6%) and locomotion (10%).

Major oscillations in spontaneous home-cage activity in C57BL/6 mice housed under constant conditions.

The mouse is the most important mammalian model in life science research and the behavior of the mouse is a key read-out of experimental interventions and genetic manipulations. To serve this purpose a solid understanding of the mouse normal behavior is a prerequisite. Using 14-19 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique, evidence is here provided for a highly significant circannual oscillation in spontaneous activity (1-2 SD of the mean, on average 65% higher during peak of highs than lows; P = 7E-50) of male and female C57BL/6 mice held under constant conditions.

Impairment of DHA synthesis alters the expression of neuronal plasticity markers and the brain inflammatory status in mice.

Docosahexaenoic acid (DHA) is a ω-3 fatty acid typically obtained from the diet or endogenously synthesized through the action of elongases (ELOVLs) and desaturases. DHA is a key central nervous system constituent and the precursor of several molecules that regulate the resolution of inflammation. In the present study, we questioned whether the impaired synthesis of DHA affected neural plasticity and inflammatory status in the adult brain.

Towards large scale automated cage monitoring - Diurnal rhythm and impact of interventions on in-cage activity of C57BL/6J mice recorded 24/7 with a non-disrupting capacitive-based technique.

Background And Aims: Automated recording of laboratory animal's home cage behavior is receiving increasing attention since such non-intruding surveillance will aid in the unbiased understanding of animal cage behavior potentially improving animal experimental reproducibility.

Material And Methods: Here we investigate activity of group held female C57BL/6J mice (mus musculus) housed in standard Individually Ventilated Cages across three test-sites: Consiglio Nazionale delle Ricerche (CNR, Rome, Italy), The Jackson Laboratory (JAX, Bar Harbor, USA) and Karolinska Insititutet (KI, Stockholm, Sweden). Additionally, comparison of female and male C57BL/6J mice was done at KI.

Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

Hutchinson-Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects.

Glial cell line-derived neurotrophic factor partially ameliorates motor symptoms without slowing neurodegeneration in mice with respiratory chain-deficient dopamine neurons.

Degeneration of midbrain dopamine neurons causes the striatal dopamine deficiency responsible for the hallmark motor symptoms of Parkinson's disease (PD). Intraparenchymal delivery of neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), is a possible future therapeutic approach. In animal PD models, GDNF can both ameliorate neurodegeneration and promote recovery of the dopamine system following a toxic insult.

Adh1 and Adh1/4 knockout mice as possible rodent models for presymptomatic Parkinson's disease.

Alcohol dehydrogenases (ADH) catalyze the reversible metabolism of many types of alcohols and aldehydes to prevent the possible toxic accumulation of these compounds. ADHs are of interest in Parkinson's disease (PD) since these compounds can be harmful to dopamine (DA) neurons. Genetic variants in ADH1C and ADH4 have been found to associate with PD and lack of Adh4 gene activity in a mouse model has recently been reported to induce changes in the DA system.

Modeling Parkinson's disease genetics: altered function of the dopamine system in Adh4 knockout mice.

Class IV alcohol dehydrogenase (ADH4) efficiently reduces aldehydes produced during lipid peroxidation, and may thus serve to protect from toxic effects of aldehydes e.g. on neurons.

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process.

Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury.

Purpose: Previous reports established that after a contusion injury to the rat spinal cord, locomotor function was enhanced by the transplantation of cells from bone marrow referred to as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). It has also been established that neural stem cells (NSCs) enhance locomotor function after transplantation into the injured rat spinal cord. However, the beneficial effects of NSCs are limited by graft-induced allodynia-like responses.

Lrrk2 and alpha-synuclein are co-regulated in rodent striatum.

LRRK2, alpha-synuclein, UCH-L1 and DJ-1 are implicated in the etiology of Parkinson's disease. We show for the first time that increase in striatal alpha-synuclein levels induce increased Lrrk2 mRNA levels while Dj-1 and Uch-L1 are unchanged. We also demonstrate that a mouse strain lacking the dopamine signaling molecule DARPP-32 has significantly reduced levels of both Lrrk2 and alpha-synuclein, while mice carrying a disabling mutation of the DARPP-32 phosphorylation site T34A or lack alpha-synuclein do not show any changes.

Inhibiting epidermal growth factor receptor improves structural, locomotor, sensory, and bladder recovery from experimental spinal cord injury.

Lack of axon regeneration in the adult CNS has been attributed partly to myelin inhibitors and the properties of astrocytes. After spinal cord injury, proliferating astrocytes not only represent a physical barrier to regenerating axons but also express and secrete molecules that inhibit nerve growth, including chondroitin sulfate proteoglycans (CSPGs). Epidermal growth factor receptor (EGFR) activation triggers astrocytes into becoming reactive astrocytes, and EGFR ligands stimulate the secretion of CSPGs as well as the formation of cribriform astrocyte arrangements that contribute to the formation of glial scars.

Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.

Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy.

Recovery from spinal cord injury in tumor necrosis factor-alpha, signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 null mice.

Tumor necrosis factor-alpha is a central cytokine involved in the regulation of the innate immune response. Signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 are second messengers mediating the Th1 and Th2-specific immune responses, respectively. We studied the outcome of spinal cord injury with respect to the locomotion and axonal regeneration in tumor necrosis factor-alpha, signal transducers and activators of transcription 4 and signal transducers and activators of transcription 6 knockout mice.