Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.

The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla.

Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents.

Exercise is widely recognized as effective for various diseases and physical disorders, including those related to brain dysfunction. However, molecular mechanisms behind the beneficial effects of exercise are poorly understood. Many physical workouts, particularly those classified as aerobic exercises such as jogging and walking, produce impulsive forces at the time of foot contact with the ground.

Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats.

In the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR.

Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons.

Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT) signaling in the prefrontal cortex (PFC) of rodents.

Application of Consistent Massage-Like Perturbations on Mouse Calves and Monitoring the Resulting Intramuscular Pressure Changes.

Massage is generally recognized to be beneficial for relieving pain and inflammation. Although previous studies have reported anti-inflammatory effects of massage on skeletal muscles, the molecular mechanisms behind are poorly understood. We have recently developed a simple device to apply local cyclical compression (LCC), which can generate intramuscular pressure waves with varying amplitudes.

Local cyclical compression modulates macrophage function and alleviates immobilization-induced muscle atrophy.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood.

Effects of Treadmill Training Combined with Serotonergic Interventions on Spasticity after Contusive Spinal Cord Injury.

Spasticity usually emerges during the course of recovery from spinal cord injury (SCI). While medications and physical rehabilitation are prescribed to alleviate spastic symptoms, the insufficiency of their effects remains an important problem to be addressed. Given the challenges associated with increasing the dose of medication, we hypothesized that a combination therapy with medication and physical rehabilitation can be effective.

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI).

Neuregulin-1 type III knockout mice exhibit delayed migration of Schwann cell precursors.

In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal.

The swimming test is effective for evaluating spasticity after contusive spinal cord injury.

Spasticity is a frequent chronic complication in individuals with spinal cord injury (SCI). However, the severity of spasticity varies in patients with SCI. Therefore, an evaluation method is needed to determine the severity of spasticity.

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.

Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model.

The crucial role of Erk2 in demyelinating inflammation in the central nervous system.

Background: Brain inflammation is a crucial component of demyelinating diseases such as multiple sclerosis. Although the initiation of inflammatory processes by the production of cytokines and chemokines by immune cells is well characterized, the processes of inflammatory aggravation of demyelinating diseases remain obscure. Here, we examined the contribution of Erk2, one of the isoforms of the extracellular signal-regulated kinase, to demyelinating inflammation.

Zbtb20 promotes astrocytogenesis during neocortical development.

Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP expression and essential factors for the specification step have remained elusive.

High mobility group nucleosome-binding family proteins promote astrocyte differentiation of neural precursor cells.

Astrocytes are the most abundant cell type in the mammalian brain and are important for the functions of the central nervous system. Although previous studies have shown that the STAT signaling pathway or its regulators promote the generation of astrocytes from multipotent neural precursor cells (NPCs) in the developing mammalian brain, the molecular mechanisms that regulate the astrocytic fate decision have still remained largely unclear. Here, we show that the high mobility group nucleosome-binding (HMGN) family proteins, HMGN1, 2, and 3, promote astrocyte differentiation of NPCs during brain development.

Paxillin is the target of c-Jun N-terminal kinase in Schwann cells and regulates migration.

During development of the peripheral nervous system (PNS), Schwann cells migrate along axons, wrapping individual axons to form a myelin sheath. This process is all mediated by the intercellular signaling between neurons and Schwann cells. As yet, little is known about the intracellular signaling mechanisms controlling these morphological changes including Schwann cell migration.

Homeobox genes Gsx1 and Gsx2 differentially regulate telencephalic progenitor maturation.

Homeobox genes Gsx1 and Gsx2 (formerly Gsh1 and Gsh2) are among the earliest transcription factors expressed in neuronal progenitors of the lateral ganglionic eminence (LGE) in the ventral telencephalon. Gsx2 is required for the early specification of LGE progenitor cells and recently has been shown to specify different LGE neuronal subtypes at distinct time points. In Gsx2 mutants, Gsx1 compensates, at least in part, for the loss of Gsx2 in the specification of LGE neuronal subtypes.

Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF-p53 pathway.

The modes of proliferation and differentiation of neural stem cells (NSCs) are coordinately controlled during development, but the underlying mechanisms remain largely unknown. In this study, we show that the protooncoprotein Myc and the tumor suppressor p19(ARF) regulate both NSC self-renewal and their neuronal and glial fate in a developmental stage-dependent manner. Early-stage NSCs have low p19(ARF) expression and retain a high self-renewal and neurogenic capacity, whereas late-stage NSCs with higher p19(ARF) expression possess a lower self-renewal capacity and predominantly generate glia.

Ascl1 is required for oligodendrocyte development in the spinal cord.

Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitors (OLPs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. How these distinct steps are controlled remains unclear.

Cross talk between notch and growth factor/cytokine signaling pathways in neural stem cells.

Precise control of proliferation and differentiation of multipotent neural stem cells (NSCs) is crucial for proper development of the nervous system. Although signaling through the cell surface receptor Notch has been implicated in many aspects of neural development, its role in NSCs remains elusive. Here we examined how the Notch pathway cross talks with signaling for growth factors and cytokines in controlling the self-renewal and differentiation of NSCs.

Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord.

During development, the three major neural cell lineages, neurons, oligodendrocytes and astrocytes, differentiate in specific temporal orders at topologically defined positions. How the timing and position of their generation are coordinately regulated remains poorly understood. Here, we provide evidence that the transcription factors Pax6, Olig2 and Nkx2.

Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord.

Neurons and oligodendrocytes are highly vulnerable to various insults, and their spontaneous replacement occurs to only a limited extent after damage in the adult spinal cord. The environment of injured tissue is thus thought to restrict the regenerative capacity of endogenous neural stem/progenitor cells; strategies for overcoming such restrictions remain to be developed. Here, we combined growth factor treatment and genetic manipulation to stimulate neurogenesis and oligodendrogenesis by endogenous progenitors in vivo.