scholarly journals Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in human and mice

2021 ◽  
Author(s):  
Zhi-Li Huang ◽  
Chang-Rui Chen ◽  
Yu-Heng Zhong ◽  
Shan Jiang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Essential Role ◽  
Physiological Arousal ◽  
Neural Circuitry ◽  
Electrophysiological Recording ◽  
Hypothalamic Nucleus ◽  
Neuronal Activation ◽  
Paraventricular Hypothalamic Nucleus

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infections or tumorigenesis. HD was traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesion of a single, even two or more wake-promoting nucleuses simultaneously did not exert serious HD. The specific nucleus and neural circuitry for HD remain unknown. Here, we observed that three patients with lesions around the paraventricular nucleus 23 of the hypothalamus (PVH) showed hypersomnolence lasting more than 20 h per day and their excessive sleep decreased with the recovery of the PVH area. Therefore, we hypothesized that the PVH might play an essential role in the occurrence of HD. Using multichannel electrophysiological recording and fiber photometry, we found that PVHvglut2 neurons were preferentially active during wakefulness. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH, PVHPDYN and PVHOT neuronal activation also exerted wakefulness. Most importantly, ablation of PVHvglut2 neurons drastically induced hypersomnia-like behaviors (30.6% reduction in wakefulness). These results indicate that dysfunctions of the PVH is crucial for physiological arousal and pathogenesis underlying HD.

scholarly journals Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation

2016 ◽  
Vol 310 (3) ◽  
pp. R275-R285 ◽  
Author(s):  
Michael A. Thomas ◽  
Vitaly Ryu ◽  
Timothy J. Bartness
Keyword(s):  
Food Deprivation ◽  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Hypothalamic Nucleus ◽  
Neuronal Activation ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Paraventricular Hypothalamic Nucleus ◽  
Ghrelin Receptor ◽  
Siberian Hamsters

The stomach-derived “hunger hormone” ghrelin increases in the circulation in direct response to time since the last meal, increasing preprandially and falling immediately following food consumption. We found previously that peripheral injection of ghrelin potently stimulates food foraging (FF), food hoarding (FH), and food intake (FI) in Siberian hamsters. It remains, however, largely unknown if central ghrelin stimulation is necessary/sufficient to increase these behaviors regardless of peripheral stimulation of the ghrelin receptor [growth hormone secretagogue receptor (GHSR)]. We injected three doses (0.01, 0.1, and 1.0 μg) of ghrelin into the third ventricle (3V) of Siberian hamsters and measured changes in FF, FH, and FI. To test the effects of 3V ghrelin receptor blockade, we used the potent GHSR antagonist JMV2959 to block these behaviors in response to food deprivation or a peripheral ghrelin challenge. Finally, we examined neuronal activation in the arcuate nucleus and paraventricular hypothalamic nucleus in response to peripheral ghrelin administration and 3V GHSR antagonism. Third ventricular ghrelin injection significantly increased FI through 24 h and FH through day 4. Pretreatment with 3V JMV2959 successfully blocked peripheral ghrelin-induced increases in FF, FH, and FI at all time points and food deprivation-induced increases in FF, FH, and FI up to 4 h. c-Fos immunoreactivity was significantly reduced in the paraventricular hypothalamic nucleus, but not in the arcuate nucleus, following pretreatment with intraperitoneal JMV2959 and ghrelin. Collectively, these data suggest that central GHSR activation is both necessary and sufficient to increase appetitive and consummatory behaviors in Siberian hamsters.

scholarly journals Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Chang-Rui Chen ◽  
Yu-Heng Zhong ◽  
Shan Jiang ◽  
Wei Xu ◽  
Lei Xiao ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Neural Circuitry ◽  
Lateral Septum ◽  
Hypothalamic Nucleus ◽  
Active Period ◽  
Vesicular Glutamate Transporter ◽  
Paraventricular Hypothalamic Nucleus ◽  
Electrophysiological Recordings ◽  
Inactive Period ◽  
Fos Expression

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

scholarly journals Paraventricular hypothalamic nucleus are essential for arousal promotion and maintenance

2021 ◽  
Author(s):  
Zhi-Li Huang ◽  
Chang-Rui Chen ◽  
Yu-Heng Zhong ◽  
Shan Jiang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Nrem Sleep ◽  
Neural Circuitry ◽  
Lateral Septum ◽  
Hypothalamic Nucleus ◽  
Population Activity ◽  
Daytime Functioning ◽  
Paraventricular Hypothalamic Nucleus ◽  
Clinical Observations ◽  
Electrophysiological Recordings

Abstract Adequate wakefulness is fundamental for proper daytime functioning. Clinical observations indicate that the paramedian region of the hypothalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Here, we found that inhibition of PVHvglut2 neurons induced 3-h increase of NREM sleep. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH neuronal activation also exerted wakefulness. Photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from NREM to wakefulness. Furthermore, using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we find arousal-dependent increases in population activity of PVHvglut2 neurons. Most importantly, ablation of PVHvglut2 neurons dramatically led mice to hypersomnia-like behaviors. These results demonstrate that PVHvglut2 neurons are essential for physiologic arousal in the hypothalamus.

scholarly journals Adjustment of Whey:Casein Ratio from 20:80 to 60:40 in Milk Formulation Affects Food Intake and Brainstem and Hypothalamic Neuronal Activation and Gene Expression in Laboratory Mice

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 658
Author(s):  
Erin L. Wood ◽  
David G. Christian ◽  
Mohammed Arafat ◽  
Laura K. McColl ◽  
Colin G. Prosser ◽  
...  
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Energy Levels ◽  
Early Gene ◽  
Hypothalamic Nucleus ◽  
Laboratory Mice ◽  
Neuronal Activation ◽  
Short Term ◽  
Animal Milk ◽  
The Impact

Adjustment of protein content in milk formulations modifies protein and energy levels, ensures amino acid intake and affects satiety. The shift from the natural whey:casein ratio of ~20:80 in animal milk is oftentimes done to reflect the 60:40 ratio of human milk. Studies show that 20:80 versus 60:40 whey:casein milks differently affect glucose metabolism and hormone release; these data parallel animal model findings. It is unknown whether the adjustment from the 20:80 to 60:40 ratio affects appetite and brain processes related to food intake. In this set of studies, we focused on the impact of the 20:80 vs. 60:40 whey:casein content in milk on food intake and feeding-related brain processes in the adult organism. By utilising laboratory mice, we found that the 20:80 whey:casein milk formulation was consumed less avidly and was less preferred than the 60:40 formulation in short-term choice and no-choice feeding paradigms. The relative PCR analyses in the hypothalamus and brain stem revealed that the 20:80 whey:casein milk intake upregulated genes involved in early termination of feeding and in an interplay between reward and satiety, such as melanocortin 3 receptor (MC3R), oxytocin (OXT), proopiomelanocortin (POMC) and glucagon-like peptide-1 receptor (GLP1R). The 20:80 versus 60:40 whey:casein formulation intake differently affected brain neuronal activation (assessed through c-Fos, an immediate-early gene product) in the nucleus of the solitary tract, area postrema, ventromedial hypothalamic nucleus and supraoptic nucleus. We conclude that the shift from the 20:80 to 60:40 whey:casein ratio in milk affects short-term feeding and relevant brain processes.

Hypothalamic paraventricular nucleus lesions do not prevent anorectic effect of exercise in male rats

1990 ◽  
Vol 259 (3) ◽  
pp. R579-R584 ◽  
Author(s):  
S. Rivest ◽  
D. Richard
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Paraventricular Nucleus ◽  
Wistar Rats ◽  
Energy Gain ◽  
Hypothalamic Paraventricular Nucleus ◽  
Male Rats ◽  
Hypothalamic Nucleus ◽  
Serum Corticosterone ◽  
Male Wistar Rats

The effects of a hypothalamic paraventricular nucleus (PVN) lesion on energy balance were investigated in exercise-trained rats. Male Wistar rats weighing initially 250 g were divided into four groups. Two groups of rats underwent a bilateral PVN lesion, whereas the two remaining groups were sham operated. The PVN lesions were done electrolytically. One group from each surgical treatment was exercised, while the other group was kept in sedentary conditions. Rats were exercised on a rodent motor-driven treadmill at moderate intensity, 1 h/day for 21 consecutive days. Food intake and body weight were measured each day during the study. At the end of the treatment period, rats were killed, and carcasses were analyzed for their energy content. Serum corticosterone was measured by a competitive protein-binding assay. Energy gain and energy intake were lower in exercised rats than in sedentary controls, regardless of whether they were sham or PVN lesioned. Concurrently, there was no difference in the energy gain between PVN-lesioned and sham-operated rats, despite the fact that PVN-lesioned rats ended the experiment with a larger body weight than the sham-lesioned animals. Serum corticosterone levels were lower in PVN-lesioned rats than in sham-lesioned rats. In conclusion, the present results indicate that the PVN, the hypothalamic nucleus predominantly controlling the pituitary-adrenal axis activity, is not a prominent structure in the regulation of energy balance in exercised male Wistar rats.

Decreased hexokinase activity in paraventricular nucleus of adult SHR and renal hypertensive rats

1988 ◽  
Vol 254 (3) ◽  
pp. R508-R512 ◽  
Author(s):  
T. L. Krukoff
Keyword(s):  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Metabolic Activity ◽  
Central Nucleus ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Medial Nucleus ◽  
Wistar Kyoto ◽  
Renal Hypertensive Rats

Metabolic activity was assessed in the brains of spontaneously hypertensive rats (SHR) using the histochemical hexokinase (HK) technique and photodensitometric analysis. Of eight regions known to play a role in cardiovascular regulation, only the paraventricular nucleus of the hypothalamus (PVH) exhibited alterations in HK activity. Significantly lower levels of HK activity in SHR than in control Sprague-Dawley and Wistar-Kyoto rats were measured in both the parvo- and magnocellular divisions of the PVH. No differences in HK activity were found in the anterior hypothalamic nucleus, posterior hypothalamic nucleus, supraoptic nucleus, subfornical organ, central nucleus of the amygdala, or the medial nucleus of the tractus solitarius of SHR. Similar results were obtained in renal hypertensive rats; furthermore, a positive correlation was found between levels of arterial pressure and densitometric readings. These latter results strongly suggest that metabolic alterations in the PVH of SHR are directly related to the increases in arterial pressure and are not due to the genetic makeup of SHR. In light of studies by others, the data from the present study have been interpreted to suggest that the decreases in metabolic activity in the PVH of the adult SHR are the result of a central attempt to bring the level of the arterial pressure down to normal levels and not to the altered activity of a region that might be acting to keep arterial pressure elevated.

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