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Click on the blue word to focus on our hypothalamic neurons expressing agouti-related peptide (AGRP), proopiomelanocortin (POMC), melanin aggregation hormone (MCH), orexin and other hormones as classical signals involved in the regulation of feeding behavior
.
In recent years, somatostatinergic neurons in the tubercle, GABAergic neurons and histaminergic neurons in the zona indeterminate are also involved in the regulation of feeding behavior
.
Acute or chronic inhibition of medial septal nucleus (MS) neurons promotes feeding behavior, a region of the brain that receives input from the hypothalamic tubercular mammillary body (TMN), a brain region containing primarily histaminergic (HA) neurons area
.
On March 25, 2022, the research team of Chen Zhong from the School of Pharmacy, Zhejiang University and Zhejiang University of Traditional Chinese Medicine published an article in the journal Current Biology, revealing a neural circuit with the potential to treat obesity: histamine neurons in the TMN area project to excitatory nerves in the MS area loop
.
Figure 1: Fiber optic calcium imaging records histaminergic neuron activity in the TMN region.
The researchers found that histaminergic neuron activity in the TMN region decreased during feeding by fiber optic calcium imaging
.
In addition, the activity of neurons in the TMN region with histaminergic projections to the MS region (hereinafter referred to as the TMN-HA→MS loop) was also significantly attenuated after eating
.
Photoinhibition of the TMN-HA→MS circuit can promote the feeding behavior of satiety mice, while activation of this neural circuit can inhibit the feeding behavior of fasting mice, suggesting that the TMN-HA→MS circuit is regulated in both directions eating behavior
.
Figure 2: Types of neurons activated in the MS region after fasting Previous studies have shown that inhibitory, cholinergic, and excitatory neurons in the MS region are all involved in regulating feeding behavior
.
This paper found that about two-thirds of the neurons activated in the MS area after fasting were excitatory neurons
.
Fiber-optic calcium imaging recordings found a rapid decrease in excitatory neurons in the MS region after eating and an increase in activity after cessation of eating
.
Chronic inhibition of this type of neurons promotes diet and increases body weight in mice
.
Virus tracing experiments showed that excitatory neurons in MS area could receive histaminergic input in TMN area, and excitatory neuron activity in MS area was enhanced after light-activated histaminergic neurons in TMN area
.
The above study found that activation of the TMN-HA→MS loop inhibited feeding, but this inhibitory effect no longer existed in the activation of excitatory neurons in the MS region
.
The injection of the histamine type 3 receptor H3R antagonist thiopiperamide in the MS area can inhibit the feeding behavior of mice.
Suppressive dietary effects elicited by activation of the HA→MS loop
.
At the same time, histamine type 2 receptor agonists were able to significantly reduce food intake in the mice
.
These results suggest that the TMN-HA→MS loop regulates feeding behavior through histamine type 2 receptors
.
Figure 3: Expression of histamine type 2 receptors in the MS region of obese mice Compared with normal mice, the expression of histamine type 2 receptors on excitatory neurons in the MS region of obese mice induced by diet was reduced
.
After specific knockdown of histamine type 2 receptor expression on excitatory neurons in the MS region by viral silencing technology, 8-week-old adult mice became rapidly obese
.
Histamine type 2 receptor agonist treatment for 42 days resulted in significant weight loss in obese mice
.
This suggests that histamine type 2 receptors on excitatory neurons in the MS region play an important role in regulating diet-related diseases
.
Overall, this paper found that the TMN-HA→MS loop is dependent on histamine type 2 receptors (rather than type 1 receptors) to bidirectionally regulate eating behavior, and activation of histamine type 2 receptors can play a role in reducing body weight and treating obesity.
effect
.
[References] 1.
https://doi.
org/10.
1016/j.
cub.
2022.
03.
010 The pictures in the text are from references
.
In recent years, somatostatinergic neurons in the tubercle, GABAergic neurons and histaminergic neurons in the zona indeterminate are also involved in the regulation of feeding behavior
.
Acute or chronic inhibition of medial septal nucleus (MS) neurons promotes feeding behavior, a region of the brain that receives input from the hypothalamic tubercular mammillary body (TMN), a brain region containing primarily histaminergic (HA) neurons area
.
On March 25, 2022, the research team of Chen Zhong from the School of Pharmacy, Zhejiang University and Zhejiang University of Traditional Chinese Medicine published an article in the journal Current Biology, revealing a neural circuit with the potential to treat obesity: histamine neurons in the TMN area project to excitatory nerves in the MS area loop
.
Figure 1: Fiber optic calcium imaging records histaminergic neuron activity in the TMN region.
The researchers found that histaminergic neuron activity in the TMN region decreased during feeding by fiber optic calcium imaging
.
In addition, the activity of neurons in the TMN region with histaminergic projections to the MS region (hereinafter referred to as the TMN-HA→MS loop) was also significantly attenuated after eating
.
Photoinhibition of the TMN-HA→MS circuit can promote the feeding behavior of satiety mice, while activation of this neural circuit can inhibit the feeding behavior of fasting mice, suggesting that the TMN-HA→MS circuit is regulated in both directions eating behavior
.
Figure 2: Types of neurons activated in the MS region after fasting Previous studies have shown that inhibitory, cholinergic, and excitatory neurons in the MS region are all involved in regulating feeding behavior
.
This paper found that about two-thirds of the neurons activated in the MS area after fasting were excitatory neurons
.
Fiber-optic calcium imaging recordings found a rapid decrease in excitatory neurons in the MS region after eating and an increase in activity after cessation of eating
.
Chronic inhibition of this type of neurons promotes diet and increases body weight in mice
.
Virus tracing experiments showed that excitatory neurons in MS area could receive histaminergic input in TMN area, and excitatory neuron activity in MS area was enhanced after light-activated histaminergic neurons in TMN area
.
The above study found that activation of the TMN-HA→MS loop inhibited feeding, but this inhibitory effect no longer existed in the activation of excitatory neurons in the MS region
.
The injection of the histamine type 3 receptor H3R antagonist thiopiperamide in the MS area can inhibit the feeding behavior of mice.
Suppressive dietary effects elicited by activation of the HA→MS loop
.
At the same time, histamine type 2 receptor agonists were able to significantly reduce food intake in the mice
.
These results suggest that the TMN-HA→MS loop regulates feeding behavior through histamine type 2 receptors
.
Figure 3: Expression of histamine type 2 receptors in the MS region of obese mice Compared with normal mice, the expression of histamine type 2 receptors on excitatory neurons in the MS region of obese mice induced by diet was reduced
.
After specific knockdown of histamine type 2 receptor expression on excitatory neurons in the MS region by viral silencing technology, 8-week-old adult mice became rapidly obese
.
Histamine type 2 receptor agonist treatment for 42 days resulted in significant weight loss in obese mice
.
This suggests that histamine type 2 receptors on excitatory neurons in the MS region play an important role in regulating diet-related diseases
.
Overall, this paper found that the TMN-HA→MS loop is dependent on histamine type 2 receptors (rather than type 1 receptors) to bidirectionally regulate eating behavior, and activation of histamine type 2 receptors can play a role in reducing body weight and treating obesity.
effect
.
[References] 1.
https://doi.
org/10.
1016/j.
cub.
2022.
03.
010 The pictures in the text are from references
