scholarly journals Functional Activation of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis

2021 ◽  
Vol 11 (4) ◽  
pp. 499
Author(s):  
Natalie N. Nawarawong ◽  
Chelsea G. Nickell ◽  
Deann M. Hopkins ◽  
James R. Pauly ◽  
Kimberly Nixon
Keyword(s):  
Alcohol Dependence ◽  
Training Session ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Male Rats ◽  
Neuronal Nuclei ◽  
Structural Recovery ◽  
Dividing Cells ◽  
Newborn Neurons ◽  
Fluorescent Immunohistochemistry

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry.

scholarly journals Recovery of Hippocampal-Dependent Learning Despite Blunting Reactive Adult Neurogenesis After Alcohol Dependence

2020 ◽  
Vol 6 (1) ◽  
pp. 83-101 ◽  
Author(s):  
Chelsea G. Nickell ◽  
K. Ryan Thompson ◽  
James R. Pauly ◽  
Kimberly Nixon
Keyword(s):  
Alcohol Dependence ◽  
Adult Neurogenesis ◽  
Alcohol Exposure ◽  
Cell Number ◽  
Male Rats ◽  
Proliferating Cells ◽  
Excessive Alcohol ◽  
Reactive Proliferation ◽  
Dependent Learning

Background: The excessive alcohol drinking that occurs in alcohol use disorder (AUD) causes neurodegeneration in regions such as the hippocampus, though recovery may occur after a period of abstinence. Mechanisms of recovery are not clear, though reactive neurogenesis has been observed in the hippocampal dentate gyrus following alcohol dependence and correlates to recovery of granule cell number. Objective: We investigated the role of neurons born during reactive neurogenesis in the recovery of hippocampal learning behavior after 4-day binge alcohol exposure, a model of an AUD. We hypothesized that reducing reactive neurogenesis would impair functional recovery. Methods: Adult male rats were subjected to 4-day binge alcohol exposure and two approaches were tested to blunt reactive adult neurogenesis, acute doses of alcohol or the chemotherapy drug, temozolomide (TMZ). Results: Acute 5 g/kg doses of EtOH gavaged T6 and T7 days post binge did not inhibit significantly the number of Bromodeoxyuridine-positive (BrdU+) proliferating cells in EtOH animals receiving 5 g/kg EtOH versus controls. A single cycle of TMZ inhibited reactive proliferation (BrdU+ cells) and neurogenesis (NeuroD+ cells) to that of controls. However, despite this blunting of reactive neurogenesis to basal levels, EtOH-TMZ rats were not impaired in their recovery of acquisition of the Morris water maze (MWM), learning similarly to all other groups 35 days after 4-day binge exposure. Conclusions: These studies show that TMZ is effective in decreasing reactive proliferation/neurogenesis following 4-day binge EtOH exposure, and baseline levels of adult neurogenesis are sufficient to allow recovery of hippocampal function.

scholarly journals Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood.

2022 ◽  
Author(s):  
Carol A. Dannenhoffer ◽  
Alex Gómez-A ◽  
Victoria Macht ◽  
Rayyanoor Jawad ◽  
E. Blake Sutherland ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Behavioral Flexibility ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Male Rats ◽  
Perineuronal Nets ◽  
Cholinergic Interneurons ◽  
Medial Pfc ◽  
Behavioral Impairments ◽  
Brain And Behavior

Background: Binge alcohol exposure during adolescence results in long-lasting alterations in brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony, and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) surround some interneurons, particularly PV+ interneurons, to further regulate cellular plasticity. The effect of AIE exposure on expression of these markers within the PFC is not well understood. Methods: The present study tested the hypothesis that AIE exposure reduces expression of PV+ and ChAT+ interneurons in the adult PFC and striatum and increases related expression of PNNs (marked by binding of Wisteria Floribunda agglutinin lectin; WFA) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off, i.g., P25-P54) or water (CON), and brain tissue was harvested in adulthood (> P80). Immunohistochemistry and co-immunofluorescence were used to assess expression of ChAT, PV, and WFA labeling within the adult PFC and striatum following AIE exposure. Results: ChAT and PV interneuron numbers in the striatum and PFC were unchanged after AIE exposure. However, WFA labeling in the PFC of AIE-exposed rats was increased compared to CON rats. Moreover, significantly more PV neurons were surrounded by WFA labeling in AIE-exposed subjects relative to controls in both PFC subregions assessed: the orbitofrontal cortex (CON = 34%; AIE = 40%) and the medial PFC (CON = 10%; AIE = 14%). Conclusions: These findings indicate that while PV interneuron expression in the adult PFC and striatum is unaltered following AIE exposure, PNNs surrounding these neurons (indicated by extracellular WFA binding) are increased. This increase in PNNs may restrict plasticity of the ensheathed neurons, thus contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.

scholarly journals Moderate prenatal alcohol exposure impairs performance by adult male rats in an object-place paired-associate task

2019 ◽  
Vol 360 ◽  
pp. 228-234 ◽  
Author(s):  
Lilliana M. Sanchez ◽  
Jonathan Goss ◽  
Jennifer Wagner ◽  
Suzy Davies ◽  
Daniel D. Savage ◽  
...  
Keyword(s):  
Adult Male ◽  
Paired Associate ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Male Rats ◽  
Prenatal Alcohol

scholarly journals Galantamine prevents and reverses neuroimmune induction and loss of adult hippocampal neurogenesis following adolescent alcohol exposure

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Victoria Macht ◽  
Ryan Vetreno ◽  
Natalie Elchert ◽  
Fulton Crews
Keyword(s):  
Cell Death ◽  
High Mobility ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Hmgb1 Protein ◽  
Immature Neurons ◽  
Environmental Milieu ◽  
Binge Ethanol Exposure

Abstract Background Binge ethanol exposure during adolescence reduces hippocampal neurogenesis, a reduction which persists throughout adulthood despite abstinence. This loss of neurogenesis, indicated by reduced doublecortin+ immunoreactivity (DCX+IR), is paralleled by an increase in hippocampal proinflammatory signaling cascades. As galantamine, a cholinesterase inhibitor, has anti-inflammatory actions, we tested the hypothesis that galantamine would prevent (study 1) or restore (study 2) AIE induction of proinflammatory signals within the hippocampus as well as AIE-induced loss of hippocampal neurogenesis. Methods Galantamine (4 mg/kg) or vehicle (saline) was administered to Wistar rats during adolescent intermittent ethanol (AIE; 5.0 g/kg ethanol, 2 days on/2 days off, postnatal day [P] 25-54) (study 1, prevention) or after AIE during abstinent maturation to adulthood (study 2, restoration). Results Results indicate AIE reduced DCX+IR and induced cleaved caspase3 (Casp3) in DCX-expressing immature neurons. Excitingly, AIE induction of activated Casp3 in DCX-expressing neurons is both prevented and reversed by galantamine treatment, which also resulted in prevention and restoration of neurogenesis (DCX+IR). Similarly, galantamine prevented and/or reversed AIE induction of proinflammatory markers, including the chemokine (C-C motif) ligand 2 (CCL2), cyclooxygenase-2 (COX-2), and high mobility group box 1 (HMGB1) protein, suggesting that AIE induction of proinflammatory signaling mediates both cell death cascades and hippocampal neurogenesis. Interestingly, galantamine treatment increased Ki67+IR generally as well as increased pan-Trk expression specifically in AIE-treated rats but failed to reverse AIE induction of NADPH-oxidase (gp91phox). Conclusions Collectively, our studies suggest that (1) loss of neurogenesis after AIE is mediated by persistent induction of proinflammatory cascades which drive activation of cell death machinery in immature neurons, and (2) galantamine can prevent and restore AIE disruptions in the hippocampal environmental milieu to then prevent and restore AIE-mediated loss of neurogenesis.

scholarly journals Changes in Cardiac Levels of Caspase-8, Bcl-2 and NT-proBNP Following 4 Weeks of Aerobic Exercise in Diabetic Rats

2017 ◽  
Vol 2 (4) ◽  
pp. 172-177
Author(s):  
Saeid Tanoorsaz ◽  
Naser Behpoor ◽  
Vahid Tadibi
Keyword(s):  
Aerobic Exercise ◽  
Cardiac Tissue ◽  
Fasting Blood Glucose ◽  
Training Session ◽  
Exercise Program ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Caspase 8

Introduction: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of caspase-8, Bcl-2, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cardiac tissue after 4 weeks of aerobic exercise in male rats with diabetes. Methods: Forty adult male rats were randomly allocated to healthy control, diabetes, control + exercise and exercise + diabetes groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg). Two weeks after injection, fasting blood glucose levels were measured. After the induction of diabetes, the exercise program was performed for 4 weeks (5 sessions per week) at a speed of 15 to 18 m/min for 25 to 44 minutes. Forty-eight hours after the last training session, the subjects were anesthetized and the heart muscle was removed. Caspase-8, Bcl-2 and NT-proBNP levels were measured by ELISA method. Results: The induction of diabetes in the control group resulted in a significant increase in caspase-8, and NT-proBNP levels while an insignificant increase was observed for Bcl-2 levels (P<0.05). In non-diabetic groups, exercise caused no changes in caspase-8, NT-proBNP and Bcl-2 (P<0.05). Exercise in diabetic groups significantly decreased NT-proBNP while no changes were observed in caspase-8 and Bcl-2 (P<0.05). Conclusion: Our findings showed that diabetes increases the pro-apoptotic and anti-apoptotic agent. In addition, 4 weeks of regular aerobic exercises can be used as a non-pharmacological strategy to reduce the complications of apoptosis in diabetic cardiomyocytes.

Early Alcohol Withdrawal Reverses the Abnormal Levels of proBDNF/mBDNF and their Receptors

2021 ◽  
Author(s):  
Li Zhou ◽  
Jing Xiong ◽  
Chang-qing Gao ◽  
Jian-jun Bao ◽  
Xin-Fu Zhou
Keyword(s):  
Serum Level ◽  
Alcohol Dependence ◽  
Alcohol Withdrawal ◽  
Neurotrophic Factor ◽  
Ethanol Exposure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blots ◽  
Time Points ◽  
Protein Levels ◽  
Chronic Ethanol Exposure

Abstract ObjectiveProlonged excessive ethanol intake impairs learning, memory and also causes brain atrophy. Brain-derived neurotrophic factor (BDNF) plays pivotal roles in the pathology of alcohol dependence. Our previous work found that chronic ethanol exposure altered the metabolism of BDNF, leading to the imbalance of proBDNF and mature BDNF (mBDNF). In this study, we hypothesized that early alcohol withdrawal would reverse the abnormal levels of proBDNF, mBDNF and their receptors.Method30 male alcohol dependence patients were recruited. Peripheral blood was sampled from all the subjects before and one week after alcohol withdrawal. The lymphocyte protein levels of proBDNF, p75NTR, sortilin and TrkB were analyzed by western blots and the serum level of mBDNF and TrkB was assayed by sandwich enzyme-linked immunosorbent assay (ELISA) at two different time points. ResultsThe levels of mBDNF and its receptor (TrkB) increased, oppositely the levels of proBDNF and its receptors (p75NTR and sortilin) decreased one week after alcohol withdrawal. ConclusionsEarly alcohol withdrawal reversed the abnormal levels of proBDNF, mBDNF and their receptors. The shift levels of proBDNF and mBDNF were both taken in the pathology of alcohol withdrawal.

scholarly journals Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder

2020 ◽  
Vol 6 (1) ◽  
pp. 47-66 ◽  
Author(s):  
Ignatius Alvarez Cooper ◽  
Kate Beecher ◽  
Fatemeh Chehrehasa ◽  
Arnauld Belmer ◽  
Selena E. Bartlett
Keyword(s):  
Alcohol Use ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Alcohol Use Disorder ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Neuroimmune System ◽  
Inflammatory Status ◽  
The Brain ◽  
Necrosis Factor

Alcohol use disorder is a pervasive and detrimental condition that involves changes in neuroplasticity and neurogenesis. Alcohol activates the neuroimmune system and alters the inflammatory status of the brain. Tumour necrosis factor (TNF) is a well characterised neuroimmune signal but its involvement in alcohol use disorder is unknown. In this review, we discuss the variable findings of TNF’s effect on neuroplasticity and neurogenesis. Acute ethanol exposure reduces TNF release while chronic alcohol intake generally increases TNF levels. Evidence suggests TNF potentiates excitatory transmission, promotes anxiety during alcohol withdrawal and is involved in drug use in rodents. An association between craving for alcohol and TNF is apparent during withdrawal in humans. While anti-inflammatory therapies show efficacy in reversing neurogenic deficit after alcohol exposure, there is no evidence for TNF’s essential involvement in alcohol’s effect on neurogenesis. Overall, defining TNF’s role in alcohol use disorder is complicated by poor understanding of its variable effects on synaptic transmission and neurogenesis. While TNF may be of relevance during withdrawal, the neuroimmune system likely acts through a larger group of inflammatory cytokines to alter neuroplasticity and neurogenesis. Understanding the individual relevance of TNF in alcohol use disorder awaits a more comprehensive understanding of TNF’s effects within the brain.

Altered hippocampal neurogenesis in adult male rats after prenatal ethanol exposure

2006 ◽  
Vol 27 (1) ◽  
pp. 100-101 ◽  
Author(s):  
Joanna H. Sliwowska ◽  
Jennifer M. Barker ◽  
Cindy Barha ◽  
Linda Ellis ◽  
Wayne Yu ◽  
...  
Keyword(s):  
Adult Male ◽  
Ethanol Exposure ◽  
Hippocampal Neurogenesis ◽  
Male Rats ◽  
Prenatal Ethanol Exposure

Vascular function in alcohol-treated pregnant and nonpregnant mice

2001 ◽  
Vol 281 (5) ◽  
pp. R1449-R1455 ◽  
Author(s):  
Jocelynn L. Cook ◽  
Yunlong Zhang ◽  
Sandra T. Davidge
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Vascular System ◽  
Prenatal Alcohol Exposure ◽  
Control Diet ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Vascular Response ◽  
Oxide Component ◽  
Pregnant Mice

The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.

scholarly journals Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala

2020 ◽  
Vol 6 (12) ◽  
pp. eaaz1050
Author(s):  
S. Khom ◽  
T. Steinkellner ◽  
T. S. Hnasko ◽  
M. Roberto
Keyword(s):  
Substance P ◽  
Alcohol Dependence ◽  
Critical Role ◽  
Alcohol Exposure ◽  
Gaba Release ◽  
Central Nucleus ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Gaba Transmission ◽  
Alcohol Dependent

Behavioral and clinical studies suggest a critical role of substance P (SP)/neurokinin-1 receptor (NK-1R) signaling in alcohol dependence. Here, we examined regulation of GABA transmission in the medial subdivision of the central amygdala (CeM) by the SP/NK-1R system, and its neuroadaptation following chronic alcohol exposure. In naïve rats, SP increased action potential–dependent GABA release, and the selective NK-1R antagonist L822429 decreased it, demonstrating SP regulation of CeM activity under basal conditions. SP induced a larger GABA release in alcohol-dependent rats accompanied by decreased NK-1R expression compared to naïve controls, suggesting NK-1R hypersensitivity which persisted during protracted alcohol withdrawal. The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol. Collectively, we report long-lasting CeA NK-1R hypersensitivity corroborating that NK-1Rs are promising targets for the treatment of alcohol use disorder.

Sign in / Sign up

Export Citation Format

Share Document