Semaphorin3F Drives Dendritic Spine Pruning Through Rho-GTPase Signaling

In humans, nonhuman primates, and rodents, the frontal cortices exhibit grey matter thinning and dendritic spine pruning that extends late into adolescence. This protracted maturation is believed to support higher cognition but may also confer psychiatric vulnerability during adolescence. Currently, little is known about how different cell types in the frontal cortex mature or whether puberty plays a role. Here, we used mice to characterize the spatial topography and adolescent development of cross-corticostriatal (cSTR) neurons that project to the dorsomedial striatum (DMS). We found that apical spine density on cSTR neurons in the medial prefrontal cortex decreased significantly between late juvenile (P29) and young adult time points (P60), with females exhibiting higher spine density than males at both ages. Adult males castrated prior to puberty onset had higher spine density compared to sham controls. Adult females ovariectomized before puberty onset showed greater variance in spine density measures on cSTR cells compared to controls, but their mean spine density did not significantly differ from sham controls. Our findings reveal that these cSTR neurons, a subtype of the broader class of intratelencephalic-type neurons, exhibit significant sex differences and suggest that spine pruning on cSTR neurons is regulated by puberty in males.

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Reduced BDNF Expression in Auditory Cortex Contributed to Neonatal Pain Induced Hearing Impairment and Dendritic Pruning Deficiency in Mice

10.21203/rs.3.rs-1084831/v1 ◽

2021 ◽

Author(s):

Nanqi Li ◽

Bing Chen ◽

Gaogan Jia ◽

Rui Xu ◽

Ying Xia ◽

...

Keyword(s):

Hearing Loss ◽

Auditory Cortex ◽

Hair Cell ◽

Hearing Impairment ◽

Dendritic Spine ◽

Bdnf Level ◽

Cochlear Function ◽

Neonatal Pain ◽

Brainstem Response ◽

Spine Pruning

Abstract Hearing loss in children is common especially in NICU with consequences of worse outcomes in speech, language, education, social functioning, cognitive abilities, and quality of life. Whether neonatal pain is link to increase risks for hearing loss remains to be explored. Here, we implemented Complete Freund's adjuvant (CFA) plantar injection and needle prick model to mimic neonatal pain in NICU during critical period of hearing development. Auditory brainstem response (ABR) test was used to determine the hearing threshold at 4w and 8w postnatal. Sufentanil and Oxycodone were used as analgesic to treat neonatal pain. Hair cell and ribbon synapse stanning were performed to detect cochlear function. Golgi-cox staining and BDNF immunofluorescence of auditory cortex were performed to determine dendritic spine pruning in auditory cortex. The dendritic pruning related protein CaMKII and Rac1/2 level were detected by western blot. We found that CFA induced neonatal pain and ABR threshold increased at 4w and 8w postnatal and the impairment were attenuated after analgesic administration. Neither the inner hair cell (IHC) nor the synapse of CFA mice was damaged in cochlear. CFA mice showed increased dendritic spine density at auditory cortex and reduced BDNF level. Furthermore, Rac1/2 and CaMKII might contributed to the disrupt dendritic spine pruning. Our study suggested that neonatal pain could induced hearing impairment in adulthood ascribed to the reduced BDNF level and AC dendritic spine pruning deficiency, optimal analgesic in early-life could beneficial for hearing development.

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Faculty Opinions recommendation of The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1102168.565513 ◽

2008 ◽

Author(s):

Pekka Lappalainen

Keyword(s):

Dendritic Spine ◽

Rho Gtpase ◽

P190 Rhogap ◽

Spine Morphogenesis

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Wnt5a modulates dendritic spine dynamics through the regulation of Cofilin via small Rho GTPase activity in hippocampal neurons

Journal of Neurochemistry ◽

10.1111/jnc.15448 ◽

2021 ◽

Author(s):

Daniela Vallejo ◽

Carolina B. Lindsay ◽

Christian González‐Billault ◽

Nibaldo C. Inestrosa

Keyword(s):

Dendritic Spine ◽

Hippocampal Neurons ◽

Rho Gtpase ◽

Gtpase Activity ◽

Spine Dynamics

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Sex and Pubertal Status Influence Dendritic Spine Density on Frontal Corticostriatal Projection Neurons in Mice

Cerebral Cortex ◽

10.1093/cercor/bhz325 ◽

2020 ◽

Vol 30 (6) ◽

pp. 3543-3557 ◽

Cited By ~ 2

Author(s):

Kristen Delevich ◽

Nana J Okada ◽

Ameet Rahane ◽

Zicheng Zhang ◽

Christopher D Hall ◽

...

Keyword(s):

Adolescent Development ◽

Dendritic Spine ◽

Cell Types ◽

Projection Neurons ◽

Specific Cell ◽

Spine Density ◽

Adult Males ◽

Puberty Onset ◽

Spatial Topography ◽

Spine Pruning

Abstract In humans, nonhuman primates, and rodents, the frontal cortices exhibit grey matter thinning and dendritic spine pruning that extends into adolescence. This maturation is believed to support higher cognition but may also confer psychiatric vulnerability during adolescence. Currently, little is known about how specific cell types in the frontal cortex mature or whether puberty plays a role in the maturation of some cell types but not others. Here, we used mice to characterize the spatial topography and adolescent development of cross-corticostriatal (cSTR) neurons that project through the corpus collosum to the dorsomedial striatum. We found that apical spine density on cSTR neurons in the medial prefrontal cortex decreased significantly between late juvenile (P29) and young adult time points (P60), with females exhibiting higher spine density than males at both ages. Adult males castrated prior to puberty onset had higher spine density compared to sham controls. Adult females ovariectomized before puberty onset showed greater variance in spine density measures on cSTR cells compared to controls, but their mean spine density did not significantly differ from sham controls. Our findings reveal that these cSTR neurons, a subtype of the broader class of intratelencephalic-type neurons, exhibit significant sex differences and suggest that spine pruning on cSTR neurons is regulated by puberty in male mice.

Download Full-text