Despite the indication that the hypothalamo-pituitary-adrenal (HPA) axis is activated during treadmill running, there have not been any studies focusing on the relationship between exercise intensity ...and region-specific neural activities in hypothalamus. To address this, rats were subjected to 30
min of running, either at middle (supra-LT, 25
m
min
−1) or low speeds (sub-LT, 15
m
min
−1), and c-Fos-(+) cells were counted and compared with control rats. Significant increases in blood glucose and lactate levels, and plasma ACTH and osmolality levels were observed during supra-LT running. Only supra-LT running significantly increased c-Fos induction in various hypothalamic regions, namely, the medial preoptic area (MPO), periventricular nucleus (Pe), suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), parvocellular division of the paraventricular nucleus (pPVN), anterior hypothalamic area (AH), arcuate nucleus (ARC) and posterior hypothalamic nucleus (PH). However, sub-LT caused no effect on c-Fos accumulation. This indicates that the hypothalamus responds uniquely to running in a threshold-like pattern distinct from the speed-dependent pattern previously reported for the medulla oblongata
Ohiwa et al., 2006a,b. In addition, these results showed a physiologic basis for mild exercise useful for establishing our minimum running stress (MRS) rat model, or the running conditions that minimize the activation of the HPA axis.
We investigated the effects of regular exercise on chronic stress-induced memory consolidation impairment and its underlying mechanism. We focused on prolactin (PRL)-modulated calcium-permeable ...(CP)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) in neurons in the CA1 stratum lacunosum-moleculare (SLM) area of the dorsal hippocampus. Regular exercise protected against memory retention defects and prevented dendritic retraction in apical distal segments of hippocampal CA1 neurons, as indicated by enhanced dendritic ramification, dendritic length, spine density, and synaptic protein levels following chronic stress. Regular exercise normalized synaptic CP-AMPAR assembly in the hippocampal CA1 SLM area, as evidenced by an enhanced ratio of GluR1 to GluR2 during chronic stress. This alteration in AMPARs was critical to memory retention, whereby memory retention was blunted by local blockage of CP-AMPARs in the SLM of naïve and exercised mice. Regular exercise improved PRL responsiveness in the hippocampal CA1 region during chronic stress, which led to increased binding of PRL to its receptor (PRLR) and PRL-dependent enhancement in phosphorylated signal transducer and activator of transcription 5 levels. The improvement in PRL responsiveness contributed to memory retention during chronic stress, as the protective action of exercise on memory persistence during stress was abolished by PRLR knockdown in the hippocampal CA1 area. Finally, in primary hippocampal cultures, repeated treatment with corticosterone led to decreased AMPAR-mediated Ca
2+
influx, which was restored by PRL treatment. The above findings suggest a protective role for exercise against chronic stress-evoked defects in memory consolidation via PRL-modulated incorporation of CP-AMPARs into hippocampal CA1 synapses.
SCOPE: There is a growing necessity for efficacious natural supplements with antioxidant effects on the brain, in particular, hippocampal function. One such compound, which also has a neuroprotective ...effect, is the carotenoid astaxanthin (ASX). Despite ASX's potential benefit to the brain, very little is known about its effect on hippocampal plasticity and cognition. Thus, we investigated the effect of ASX on adult hippocampal neurogenesis (AHN) and spatial memory using a mouse model. METHODS AND RESULTS: Dose‐response was examined in mice fed ASX‐supplemented diets (0, 0.02, 0.1, and 0.5%) to define the effect of ASX on AHN. In conjunction with AHN results, hippocampus‐dependent cognitive function was assessed. We delineated molecular mechanisms associated with ASX‐enhanced AHN using DNA microarray analysis. Results revealed that ASX enhanced cell proliferation and survival at 0.1% and 0.5% doses. Newborn mature neurons were higher only with 0.5% ASX, which also enhanced spatial memory. Transcriptomic profiling revealed potential AHN‐associated molecules (Prl, Itga4, and Il4) that were ASX induced. Their downstream factors, identified through Ingenuity Pathway Analysis, were positively correlated with ASX‐induced increases in spatial memory. CONCLUSION: ASX supplementation enhanced AHN and spatial memory, and a DNA microarray approach provided, for the first time, novel molecular insights into ASX action.
Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an ...abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (
N-{(1S)-1-6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinylcarbonyl}-2,2-dimethylpropyl)-
N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming stress were attenuated with prior administration of an OX-2R antagonist. These results suggest that swimming stress facilitates ACTH release, at least in part via activation of OX-2R.
This study investigates the anti-fatigue effects of Acanthopanax sieboldianus (A. sieboldianus) at various exercise intensities. Two experiments were conducted in 18 Sprague-Dawley rats. In ...Experiment 1, a three-stage increment test (15 m/min for 5 min, and 20 m/min for 5 min and 25 m/min for 10 min) was performed using a treadmill. In Experiment 2, a 10-min swimming test was conducted. Blood samples were extracted from each rat before, during and after the exercises and the blood concentrations of lactate and glucose measured. In both experiments, water (control) or A. sieboldianus solution (ASS) was administered orally using a zonde 30 min before the exercise. In the swimming test, ASS administration significantly decreased the blood lactate level measured at the end of the exercise and 5 min post-exercise relative to the water group, although the two groups did not differ significantly in the treadmill test. Our study demonstrates that a single oral administration of A. sieboldianus prior to high-intensity exercise significantly decreases the blood lactate concentration suggesting that A. sieboldianus has an intrinsic anti-fatigue effect.
In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis ...and cognitive functions, in conjunction with hippocampal brain‐derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR‐enhanced hippocampal functions; a high‐throughput whole‐genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11‐fold compared to WR, resulting in muscular adaptation for the fast‐twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up‐regulated (>1.5‐fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down‐regulated (<0.75‐fold change) genes. Functional categorization using both pathway‐ or specific‐disease‐state‐focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down‐regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary‐RWR‐related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions.
e12206
New information on the voluntary RWR influenced transcriptome in rat hippocampus. Selected gene candidates may be a critical role in the development of hippocampal adaptations in RWR.
Expression of the inducible transcription factor c-Fos was mapped in the rat medulla oblongata to identify the brain areas respond to different running speeds. Rats were subjected to 30
min of ...running, either at high speed, low speed or just sitting on a treadmill (control). Blood lactate levels were measured to confirm the physiological impact of different exercise intensities. The number of c-Fos-ir cells was counted and their spatial distributions were mapped through the rostral to the caudal level in the medulla. A statistically significant exercise intensity-dependent induction of c-Fos was observed in the nucleus of the solitary tract (NTS) and caudal ventrolateral medulla (CVL) in the medulla. Further, c-Fos induction was more predominant in the caudal part of each nucleus. The present data clearly show that different running speeds cause differential activation of each nucleus in the medulla, and in particular, the caudal parts of the NTS and the CVL are the most responsive to speed changes. The present study identifies brain areas newly found to be responsive to changes in running speed. These findings are likely to be particularly helpful in studies of specific neural circuits and their functions in response to different running speeds.
l
-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of
l
-carnitine ...administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that
l
-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with
l
-carnitine administration (1250 mg·kg
−1
·day
−1
) group, and pair-fed group adjusted hindlimb suspension.
l
-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition,
l
-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that
l
-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that
l
-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that
l
-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.
Since running accompanied with blood lactate accumulation stimulates the release of adrenocorticotropic hormone (ACTH), running above the lactate threshold (LT) acts as stress (running stress). To ...examine whether A1/A2 noradrenergic neurons that project to the hypothalamus activate under running stress, c-Fos immunohistochemistry was used to compare the effects of running with or without stress response on A1/A2 noradrenergic neurons. Blood lactate and plasma ACTH concentrations significantly increased in the running stress group, but not in the running without stress response and control groups, confirming different physiological impacts between different intensity of running with or without stress. Running stress markedly increased c-Fos accumulation in the A1/A2 noradrenergic neurons. Running without stress response also induced a significant increase in c-Fos expression in the A1/A2 noradrenergic neurons, and the percentage of the increase was smaller than that of running stress. The extent of c-Fos expression in the A1/A2 noradrenergic neurons correlates with exercise intensity, signifying that this neuronal activation is running speed-dependent. We thus suggest that A1/A2 noradrenergic neurons are activated in response to not only running stress, but also to other physiological running, enhanced by non-stressful running. These findings will be helpful in studies of specific neurocircuits and in identifying their functions in response to running at different intensities.
Human ultra-weak photon emission (UPE) is related to the activity of respiratory chain and oxygen consumption. Investigations on UPE and its response to exercise are almost non existent. Since human ...UPE is an indicator of reactive oxygen species (ROS) levels, we used exercises as a model to study UPE. To continue the research on the relationship between human UPE and exercise, it was decided to carry out measurements of UPE in response to different exercise modes with 20 healthy male subjects. The performed exercises were wrist curls with a dumbbell and indoor cycling. Regarding wrist curl exercises, 70% of the subjects for the first exercise and 65% for the second exercise did not show any significant changes in UPE. Also, the statistical analysis did not show significant changes of the UPE levels. In terms of cycling exercise, 85% of subjects did not show any significant increase of UPE. The gathered data showed that a majority of the subjects didn't show an increase of the UPE during both types of exercises. Our results imply that the UPE is not only affected by oxygen consumption, but also by the intensity, the type of exercise, and the physiology of the subject.
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