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  1. Article: Hypothalamic Orexinergic Neurons Projecting to the Mesencephalic Locomotor Region Are Activated by Voluntary Wheel Running Exercise in Rats.

    Narai, Emi / Watanabe, Tatsuo / Koba, Satoshi

    Yonago acta medica

    2024  Volume 67, Issue 1, Page(s) 52–60

    Abstract: Background: Cardiovascular changes during exercise are regulated by a motor volitional signal, called central command, which originates in the rostral portions of the brain and simultaneously regulates somatomotor and autonomic nervous systems. Whereas ... ...

    Abstract Background: Cardiovascular changes during exercise are regulated by a motor volitional signal, called central command, which originates in the rostral portions of the brain and simultaneously regulates somatomotor and autonomic nervous systems. Whereas we recently elucidated mesencephalic locomotor region (MLR) neurons projecting to the rostral ventrolateral medulla as a crucial component of the central circuit responsible for transmitting central command signals, upstream circuits that regulate the MLR neurons remain unknown. Orexinergic neurons, which primarily originate from the perifornical area (PeFA) of the hypothalamus and reportedly play roles in eliciting locomotion and elevating sympathetic activity, send axonal projection to the MLR. The knowledge led us to investigate whether central command signals are relayed through orexinergic neurons projecting to the MLR.
    Methods: We performed anterograde transsynaptic tagging with AAV1 encoding Cre to confirm the presence of MLR neurons postsynaptic to the PeFA in rats. We also conducted retrograde neural tracing with retrograde AAV, combined with immunohistochemical staining, to examine the excitability of MLR-projecting orexinergic neurons in rats that were allowed to freely run on the wheel for 90 min.
    Results: A significant number of MLR neurons were labeled with Cre, indicating that PeFA neurons make synaptic contacts with MLR neurons. Moreover, immunoreactivities of Fos, a marker of neuronal excitation, were found in many MLR-projecting orexinergic neurons by voluntary wheel running exercise, compared to non-exercising control rats, especially in the intermediate-posterior, rather than anterior, and medial, rather than lateral, portions within the orexinergic neuron-distributing domain.
    Conclusion: The findings suggest that specifically located orexinergic neurons transmit central command signals onto the MLR for running exercise. Elucidating the role of these MLR-projecting orexinergic neurons in somatomotor control and autonomic cardiovascular control deserves further study to unveil central circuit mechanisms responsible for central command function.
    Language English
    Publishing date 2024-01-12
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 840719-8
    ISSN 1346-8049 ; 0513-5710
    ISSN (online) 1346-8049
    ISSN 0513-5710
    DOI 10.33160/yam.2024.02.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Orexinergic neurons contribute to autonomic cardiovascular regulation for locomotor exercise.

    Narai, Emi / Yoshimura, Yuki / Honaga, Takaho / Mizoguchi, Hiroyuki / Yamanaka, Akihiro / Hiyama, Takeshi Y / Watanabe, Tatsuo / Koba, Satoshi

    The Journal of physiology

    2024  

    Abstract: While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid ...

    Abstract While the hypothalamic orexinergic nervous system is established as having a pivotal role in the long-term regulation of various organismic functions, including wakefulness, metabolism and hypertensive states, whether this system contributes to the rapid autonomic cardiovascular regulation during physical activity remains elusive. This study aimed to elucidate the role of the orexinergic nervous system in transmitting volitional motor signals, i.e. central command, to drive somatomotor and sympathetic cardiovascular responses. We first found that this system is activated by voluntary locomotor exercise as evidenced by an increased expression of Fos, a marker of neural activation, in the orexinergic neurons of Sprague-Dawley rats engaged in spontaneous wheel running. Next, using transgenic Orexin-Cre rats for optogenetic manipulation of orexinergic neurons, we found that optogenetic excitation of orexinergic neurons caused sympathoexcitation on a subsecond timescale under anaesthesia. In freely moving conscious rats, this excitatory stimulation rapidly elicited exploration-like behaviours, predominantly locomotor activity, along with pressor and tachycardiac responses. Meanwhile, optogenetic inhibition of orexinergic neurons during spontaneous wheel running immediately suppressed locomotor activities and blood pressure elevation without affecting basal cardiovascular homeostasis. Taken together, these findings demonstrate the essential role of the orexinergic nervous system in the central circuitry that transmits central command signals for locomotor exercise. This study not only offers insights into the brain circuit mechanisms precisely regulating autonomic cardiovascular systems during voluntary exercise but also likely contributes to our understanding of brain mechanisms underlying abnormal cardiovascular adjustments to exercise in pathological conditions, such as hypertension. KEY POINTS: The hypothalamic orexinergic nervous system plays various roles in the long-term regulation of autonomic and endocrine functions, as well as motivated behaviours. We present a novel, rapid role of the orexinergic nervous system, revealing its significance as a crucial substrate in the brain circuit mechanisms that coordinate somatomotor and autonomic cardiovascular controls for locomotor exercise. Our data demonstrate that orexinergic neurons relay volitional motor signals, playing a necessary and sufficient role in the autonomic cardiovascular regulation required for locomotor exercise in rats. The findings contribute to our understanding of how the brain precisely regulates autonomic cardiovascular systems during voluntary exercise, providing insights into the central neural mechanisms that enhance physical performance moment-by-moment during exercise.
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP285791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A brainstem monosynaptic excitatory pathway that drives locomotor activities and sympathetic cardiovascular responses.

    Koba, Satoshi / Kumada, Nao / Narai, Emi / Kataoka, Naoya / Nakamura, Kazuhiro / Watanabe, Tatsuo

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 5079

    Abstract: Exercise including locomotion requires appropriate autonomic cardiovascular adjustments to meet the metabolic demands of contracting muscles, yet the functional brain architecture underlying these adjustments remains unknown. Here, we demonstrate ... ...

    Abstract Exercise including locomotion requires appropriate autonomic cardiovascular adjustments to meet the metabolic demands of contracting muscles, yet the functional brain architecture underlying these adjustments remains unknown. Here, we demonstrate brainstem circuitry that plays an essential role in relaying volitional motor signals, i.e., central command, to drive locomotor activities and sympathetic cardiovascular responses. Mesencephalic locomotor neurons in rats transmit central command-driven excitatory signals onto the rostral ventrolateral medulla at least partially via glutamatergic processes, to activate both somatomotor and sympathetic nervous systems. Optogenetic excitation of this monosynaptic pathway elicits locomotor and cardiovascular responses as seen during running exercise, whereas pathway inhibition suppresses the locomotor activities and blood pressure elevation during voluntary running without affecting basal cardiovascular homeostasis. These results demonstrate an important subcortical pathway that transmits central command signals, providing a key insight into the central circuit mechanism required for the physiological conditioning essential to maximize exercise performance.
    MeSH term(s) Animals ; Brain Stem ; Cardiovascular System ; Locomotion/physiology ; Medulla Oblongata ; Rats ; Sympathetic Nervous System/physiology
    Language English
    Publishing date 2022-08-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-32823-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Accelerometer-Based Monitoring of Upper Limb Movement in Older Adults With Acute and Subacute Stroke.

    Narai, Emi / Hagino, Hiroshi / Komatsu, Taiki / Togo, Fumiharu

    Journal of geriatric physical therapy (2001)

    2016  Volume 39, Issue 4, Page(s) 171–177

    Abstract: Background and purpose: Use of the affected extremity during daily life is important if disuse atrophy is to be prevented after stroke. This study examined whether objectively measured real-world upper limb movement is associated with the amount of use ... ...

    Abstract Background and purpose: Use of the affected extremity during daily life is important if disuse atrophy is to be prevented after stroke. This study examined whether objectively measured real-world upper limb movement is associated with the amount of use of the affected upper limb, as assessed by a standardized assessment tool in older adults with acute or subacute stroke. This study also examined whether the real-world upper limb movement is associated with the extent of impairment of upper and lower extremities.
    Methods: The participants were 19 older adults with hemiparesis from acute or subacute stroke [17 (7) days after the stroke]. All the participants wore 3 accelerometers-1 on each wrist (bilateral accelerometry) and 1 on the waist-throughout a 24-hour period. They were interviewed about use of their upper limb in the real-world setting using a Motor Activity Log. Functions of the affected upper limb or upper and lower limbs were assessed using the National Institute of Health Stroke Scale, the Brunnstrom Recovery Stage (BRS), the Simple Test for Evaluating Hand Function, and the Functional Independence Measure tests.
    Results and discussion: Movement counts measured with the wrist accelerometer on the affected upper limb (unilateral accelerometry) over 24 hours and during the 12-hour daytime period (08:00 to 20:00) were significantly correlated with scores for affected upper limb use (the Motor Activity Log) and functions (the upper extremity BRS and the affected side Simple Test for Evaluating Hand Function), upper and lower extremity functions (the National Institute of Health Stroke Scale, the lower extremity BRS, and the motor Functional Independence Measure), and step counts measured over the same period. To estimate the affected upper limb use or disuse, we subtracted the movement counts of the unaffected upper limb from those of the affected upper limb. As a result, the subtracted counts over 24 hours and during the 12-hour daytime period were only related to scores for affected upper limb use and functions.
    Conclusions: Bilateral accelerometry for monitoring upper limb movements in a real-world setting might be useful to clinicians for objective assessment of affected upper limb use or disuse and function among older adults with hemiparesis from acute or subacute stroke.
    Language English
    Publishing date 2016-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2250801-6
    ISSN 2152-0895 ; 1539-8412
    ISSN (online) 2152-0895
    ISSN 1539-8412
    DOI 10.1519/JPT.0000000000000067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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