Sexually dimorphic prelimbic cortex mechanisms play a role in alcohol dependence: protection by endostatin

Avchalumov, Yosef; Kreisler, Alison D.; Xing, Nancy; Shayan, Amin A; Bharadwaj, Tejash; Watson, Jacob R; Sibley, Britta D.; Somkuwar, Sucharita S.; Trenet, Wulfran; Olia, Sumaiya; Piña‐Crespo, Juan C.; Roberto, Marisa; Mandyam, Chitra D.

doi:10.1038/s41386-021-01075-6

Cited by 5 publications

(5 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 91%

“…Regarding non-neuronal correlates, our initial studies showed reactive oligodendrogenesis in the mPFC during protracted abstinence following CIE-induced dependence in both sexes [23,[100][101][102]. The reactive oligodendrogenesis was associated with enhanced expression of the endothelial cell-specific angiogenesis marker PECAM-1 in the mPFC in both sexes [101,102]. Treatment with the anti-angiogenic drug endostatin reduced PECAM-1 expression in both sexes but reduced relapse to drinking in female rats without affecting drinking in males and, in parallel, prevented the neuronal adaptations associated with the relapse of ethanol drinking in females [102].…”

Section: Discussionmentioning

confidence: 99%

“…The reactive oligodendrogenesis was associated with enhanced expression of the endothelial cell-specific angiogenesis marker PECAM-1 in the mPFC in both sexes [101,102]. Treatment with the anti-angiogenic drug endostatin reduced PECAM-1 expression in both sexes but reduced relapse to drinking in female rats without affecting drinking in males and, in parallel, prevented the neuronal adaptations associated with the relapse of ethanol drinking in females [102]. In this current study, valcyte did not affect the number of progenitors in the mPFC, suggesting that progenitors in this region did not play a role in the reinstatement of ethanol seeking behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of Iba-1 (protein expressed in macrophages and microglial cells)-labeled microglial cells in the prelimbic cortex of the mPFC and hilus of the DG was performed using a previously published protocol [102]. Zeiss Axiophot AxioImager A2 microscope was used to view the cells, and Neurolucida (MicroBrightField) was used to create three-dimensional (3D) tracings and Sholl analysis (Figure 5a-c).…”

Section: Multiplex Cytokine Immunoassaysmentioning

confidence: 99%

See 3 more Smart Citations

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Nonoguchi,

Jin,

Narreddy

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Multiplex Cytokine Immunoassaysmentioning

confidence: 99%

See 2 more Smart Citations

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Nonoguchi,

Jin,

Narreddy

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…There is a large gap in our understanding of the structure and function of the female mPFC, and emerging evidence supports the notion of at least some degree of functional differentiation of the mPFC between males and females [for review, see (Laine et al, 2024)]. Additionally, recent work has uncovered important sex differences in ethanol-induced physiological neuroadaptations in the mPFC (Avchalumov et al, 2021; Hughes et al, 2021; Joffe et al, 2020). One potential reason for this is that female rats require higher levels of intoxication to reach a similar level of behavioral impairment compared to males (Glover et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons

Przybysz,

Shillinglaw,

Wheeler

et al. 2024

Preprint

View full text Add to dashboard Cite

Chronic ethanol exposure produces neuroadaptations in the medial prefrontal cortex (mPFC) which facilitate the maladaptive behaviors interfering with recovery from alcohol use disorder. Despite evidence that different cortico-subcortical projections play distinct roles in behavior, few studies have examined the physiological effects of chronic ethanol at the circuit level. The rostromedial tegmental nucleus (RMTg) is a GABAergic midbrain region involved in aversive signaling and is functionally altered by chronic ethanol exposure. Our recent work identified a dense input from the mPFC to the RMTg, yet the effects of chronic ethanol exposure on this circuitry is unknown. In the current study, we examined physiological changes after chronic ethanol exposure in prelimbic (PL) and infralimbic (IL) mPFC neurons projecting to the RMTg. Adult male Long-Evans rats were injected with fluorescent retrobeads into the RMTg and rendered dependent using a 14-day chronic intermittent ethanol (CIE) vapor exposure paradigm. Whole-cell patch-clamp electrophysiological recordings were performed in fluorescently-labeled (RMTg-projecting) and -unlabeled (projection-undefined) layer 5 pyramidal neurons 7-10 days following ethanol exposure. CIE significantly increased intrinsic excitability as well as excitatory and inhibitory synaptic drive in RMTg-projecting IL neurons. In contrast, no lasting changes in excitability were observed in RMTg-projecting PL neurons, although a CIE-induced reduction in excitability was observed in projection-undefined PL neurons. CIE also increased excitatory synaptic drive in RMTg-projecting PL neurons. These data uncover novel subregion- and circuit-specific neuroadaptations in the mPFC following chronic ethanol exposure and reveal that the IL mPFC-RMTg projection is uniquely vulnerable to long-lasting effects of chronic ethanol.

show abstract

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2023

Current Topics in Behavioral Neurosciences

View full text Add to dashboard Cite

Sexually dimorphic prelimbic cortex mechanisms play a role in alcohol dependence: protection by endostatin

Cited by 5 publications

References 83 publications

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons

Synaptic Effects Induced by Alcohol

Contact Info

Product

Resources

About