Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Houtz, Jessica; Liao, Guey-Ying; An, Juan Ji; Xu, Baoji

doi:10.1073/pnas.2017218118

Cited by 22 publications

(24 citation statements)

References 50 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we do not rule out the possibility that PVH BDNF and PVH TrkB neurons form distinct neural circuits and project to other brain regions to suppress appetite. These questions can be addressed in future studies using projection-specific gene deletion and projection-specific neuronal activation ( An et al, 2020 ; Houtz et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Body composition was measured using a MinispecLF-50/mq 7.5 NMR Analyzer (Brucker Optics). A comprehensive lab animal monitoring system (CLAMS; Columbus Instruments) was used to obtain measurements of locomotor activity, oxygen consumption rate (VO 2 ), and CO 2 production rate (VCO 2 ) at thermoneutrality (30°C) as described previously ( Houtz et al, 2021 ). Mice were first acclimated to metabolic chambers for at least 24 h. Afterwards, an additional 24 h was used for baseline data collection of locomotor activity, VO 2 , and VCO 2 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Rapid and Lasting Effects of Activating BDNF-Expressing PVH Neurons on Energy Balance

2022

eNeuro

Self Cite

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), are implicit in causing obesity. Mutations that reduce BDNF and TrkB expression are associated with obesity in humans and mice. Recently, it was reported that Bdnf gene deletion in the neurons of the paraventricular hypothalamus (PVH) caused positive energy balance and severe obesity in the form of hyperphagia, impaired adaptive thermogenesis, and decreased energy expenditure. Thus, we hypothesize that activation of these neurons will have the opposite effect and provide an opportunity for long-lasting obesity treatment. To specifically activate BDNF-expressing PVH (PVH BDNF ) neurons, we injected Cre-dependent adeno-associated virus (AAV) expressing the excitatory DREADD hM3Dq bilaterally into the PVH of Bdnf 2A-Cre/+ knock-in mice and then administered clozapine-N-oxide (CNO). Using this technique, we demonstrated that acute activation of these neurons rapidly decreased normal nocturnal feeding and fasting-induced feeding in male and female mice. At thermoneutral temperatures, acute activation also rapidly increased adaptive thermogenesis, increased core body temperature, increased locomotion, increased energy expenditure, and decreased respiratory exchange ratio (RER) in male and female mice. These observations indicate that acute stimulation of PVH BDNF neurons promotes negative energy balance and weight loss. However, the rapid decrease in RER after activation of PVH BDNF neurons was followed by a delayed and prolonged increase in RER that remained elevated for 3 d in female mice. Thus, although acute activation of PVH BDNF neurons promotes negative energy balance in the short term, long-term effects of activation include sexually dimorphic overcompensatory mechanisms that may promote positive energy balance in female mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rapid and Lasting Effects of Activating BDNF-Expressing PVH Neurons on Energy Balance

2022

eNeuro

Self Cite

View full text Add to dashboard Cite

show abstract

“…These effector-specific efferent pathways would permit different threshold temperatures to initiate thermoregulatory effector responses observed during ambient cooling (McAllen et al, 2010). Supporting this view, a recent study showed that a DMH → rMR projection neuron subgroup that expresses the TrkB neurotrophin receptor drives BAT thermogenesis, but not cardiovascular responses (Houtz et al, 2021). More molecular markers to identify each DMH efferent neuronal subgroups will be determined by future studies.…”

Section: Hypothalamomedullary Sympathetic Pathwaysmentioning

confidence: 88%

Central sympathetic network for thermoregulatory responses to psychological stress

Nakamura

Morrison

2022

Autonomic Neuroscience

View full text Add to dashboard Cite

In mammals, many types of psychological stressors elicit a variety of sympathoexcitatory responses paralleling the classic fight-or-flight response to a threat to survival, including increased body temperature via brown adipose tissue thermogenesis and cutaneous vasoconstriction, and increased skeletal muscle blood flow via tachycardia and visceral vasoconstriction. Although these responses are usually supportive for stress coping, aberrant sympathetic responses to stress can lead to clinical issues in psychosomatic medicine. Sympathetic stress responses are mediated mostly by sympathetic premotor drives from the rostral medullary raphe region (rMR) and partly by those from the rostral ventrolateral medulla (RVLM). Hypothalamomedullary descending pathways from the dorsomedial hypothalamus (DMH) to the rMR and RVLM mediate important, stress-driven sympathoexcitatory transmission to the premotor neurons to drive the thermal and cardiovascular responses. The DMH also likely sends an excitatory input to the paraventricular hypothalamic nucleus to stimulate stress hormone release. Neurons in the DMH receive a stress-related excitation from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT) in the ventromedial prefrontal cortex. By connecting the corticolimbic emotion circuit to the central sympathetic and somatic motor systems, the DP/DTT → DMH pathway plays as the primary mediator of the psychosomatic signaling that drives a variety of sympathetic and behavioral stress responses. These brain regions together with other stress-related regions constitute a central neural network for physiological stress responses. This network model is relevant to understanding the central mechanisms by which stress and emotions affect autonomic regulations of homeostasis and to developing new therapeutic strategies for various stress-related disorders. muscles and the nervous system, which boosts physical and neural performance (Bishop, 2003). Simultaneously, stress-induced elevations of blood pressure and heart rate (i.e., cardiovascular responses) increase the supply of oxygen and energy sources (sugars and fatty acids) to skeletal muscles, thermogenic organs and the central nervous system. Another major sympathetic response to psychological stress is cutaneous Abbreviations: BAT, brown adipose tissue; CRH, corticotropin-releasing hormone; dDMH, dorsal part of the dorsomedial hypothalamus; dlPAG, dorsolateral subnucleus of the periaqueductal grey;

show abstract

“…The DMH is involved in the regulation of a variety of body life activities, including feeding [17,[27][28][29], food expectations [30], stress [19,31], metabolism [32,33], and locomotion activities [18]. In recent years, studies of the DMH in various functions have increased.…”

Section: Discussionmentioning

confidence: 99%

Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep–Wake States in Response to Changes in Ambient Temperature in Mice

Zhang

Sun

et al. 2022

IJMS

View full text Add to dashboard Cite

Good sleep quality is essential for maintaining the body’s attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep–wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been reported to be involved in thermoregulation. It also receives projection from the preoptic area, which is an important region for sleep and energy homeostasis and the suprachiasmatic nucleus—a main control area of the clock rhythm. Therefore, we hypothesized that the DMH plays an important role in the regulation of sleep related to ambient temperatures. In this study, we found that cold exposure (24/20/16/12 °C) increased wakefulness and decreased non–rapid eye movement (NREM) sleep, while warm exposure (32/36/40/44 °C) increased NREM sleep and decreased wakefulness compared to 28 °C conditions in wild-type mice. Then, using non-specific and specific apoptosis, we found that lesions of whole DMH neurons and DMH γ–aminobutyric acid (GABA)-ergic neurons induced by caspase-3 virus aggravated the fluctuation of core body temperature after warm exposure and attenuated the change in sleep–wake behaviors during cold and warm exposure. However, chemogenetic activation or inhibition of DMH GABAergic neurons did not affect the sleep–wake cycle. Collectively, our findings reveal an essential role of DMH GABAergic neurons in the regulation of sleep–wake behaviors elicited by a change in ambient temperature.

show abstract

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Cited by 22 publications

References 50 publications

Rapid and Lasting Effects of Activating BDNF-Expressing PVH Neurons on Energy Balance

Rapid and Lasting Effects of Activating BDNF-Expressing PVH Neurons on Energy Balance

Central sympathetic network for thermoregulatory responses to psychological stress

Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep–Wake States in Response to Changes in Ambient Temperature in Mice

Contact Info

Product

Resources

About