Collapsin response mediator protein 4 affects the number of tyrosine hydroxylase-immunoreactive neurons in the sexually dimorphic nucleus in female mice

2013 ◽  
Vol 73 (7) ◽  
pp. 502-517 ◽  
Author(s):  
Takashi Iwakura ◽  
Miyuki Sakoh ◽  
Atsuhiro Tsutiya ◽  
Naoya Yamashita ◽  
Akiko Ohtani ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Sexually Dimorphic ◽  
Collapsin Response Mediator Protein ◽  
Female Mice ◽  
Mediator Protein ◽  
Sexually Dimorphic Nucleus

scholarly journals Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules

Zygote ◽  
2021 ◽  
pp. 1-12
Author(s):  
Zhen Jin ◽  
Hua-Feng Shou ◽  
Jin-Wei Liu ◽  
Shan-Shan Jiang ◽  
Yan Shen ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Spindle Microtubule ◽  
Collapsin Response Mediator Protein ◽  
Microtubule Severing ◽  
Structural Support ◽  
Mediator Protein ◽  
Spindle Microtubules ◽  
Transportation Routes ◽  
Normal Meiosis

Abstract Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue

2015 ◽  
Vol 9 (9-10) ◽  
pp. 817-831 ◽  
Author(s):  
Daniel Martins-de-Souza ◽  
Juliana S. Cassoli ◽  
Juliana M. Nascimento ◽  
Kenneth Hensley ◽  
Paul C. Guest ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Collapsin Response Mediator Protein ◽  
Protein Interactome ◽  
Mediator Protein ◽  
Partner Proteins

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

A prolactin-dependent sexually dimorphic mechanism of migraine chronification

Cephalalgia ◽  
2021 ◽  
pp. 033310242110398
Author(s):  
Daigo Ikegami ◽  
Edita Navratilova ◽  
Xu Yue ◽  
Aubin Moutal ◽  
Caroline M Kopruszinski ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Dopamine Receptor Agonist ◽  
Sexually Dimorphic ◽  
Down Regulation ◽  
Female Mice ◽  
Cutaneous Allodynia

Objective Determination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms. Background The majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective. Methods Medication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms. Results PRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females. Interpretation We identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.

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