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 Second hits exacerbate alcohol-related organ damage: an update

2020 ◽  
Vol 56 (1) ◽  
pp. 8-16
Author(s):  
Natalia A Osna ◽  
Murali Ganesan ◽  
Devanshi Seth ◽  
Todd A Wyatt ◽  
Srivatsan Kidambi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcohol Exposure ◽  
Organ Damage ◽  
Lifestyle Factor ◽  
Matrix Stiffness ◽  
Reactive Aldehydes ◽  
Wide Range ◽  
Excessive Alcohol ◽  
The Impact

Abstract Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled ‘Second hits in alcohol-related organ damage’.

Modulation of neurogenesis and selected neuropeptides expression in the hypothalamus of rats exposed to neuroleptic

2016 ◽  
Vol 4 ◽  
pp. 23-35
Author(s):  
Ewa Rojczyk ◽  
Artur Pałasz
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Adult Neurogenesis ◽  
Male Rats ◽  
Rt Pcr ◽  
Immunohistochemical Assay ◽  
Food Intake Regulation ◽  
Monoamine Receptors ◽  
Intake Regulation

Patients treated with neuroleptics suffer from significant weight gain. Hypothalamus consists of neuronal circuits responsible for food intake regulation. Moreover, last finding suggest that adult neurogenesis occurs in the hypothalamus, which could play a role in the energy expenditure control. Considering that neuroleptics affect neural formation in the canonical neurogenic sites, we made a hypothesis that they could modulate hypothalamic neurogenesis and change expression of orexigenic/anorexigenic neuropeptides and their receptors. Experiments were carried out on adult male rats injected intraperitoneally for 1 or 28 days by the neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform RT-PCR reaction and also whole brains were sliced for immunohistochemical assay. We observed that antipsychotics administered chronically supported the origin of newborn cells (Ki67 +) in the hypothalamic regions and affect the number of DCX-positive immature neurons. Furthermore, they have a distinct ability to upregulate preproorexin and orexin A expression and to increase the level of some anorexigenic factors (POMC, α-MSH), at the same time strongly decreasing nesfatin-1 signalling. Our results highlight the role of neuroleptics as potential modulators of the hypothalamic neurogenesis and contribute to better understanding the mechanisms of their side effects. They also underline the complexity of interplay between monoamine receptors, hypothalamic peptidergic pathways and adult neurogenesis which has putative but possible pharmacological applications.

scholarly journals Bioinformatics identification and pharmacological validation of Kcnn3/KCa2 channels as a mediator of negative affective behaviors and excessive alcohol drinking in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Audrey E. Padula ◽  
Jennifer A. Rinker ◽  
Marcelo F. Lopez ◽  
Megan K. Mulligan ◽  
Robert W. Williams ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Mood Disorders ◽  
Alcohol Drinking ◽  
Heavy Drinking ◽  
Alcohol Exposure ◽  
Sk Channel ◽  
Affective Behaviors ◽  
Positive Modulator ◽  
Excessive Alcohol ◽  
Alcohol Dependent

AbstractMood disorders are often comorbid with alcohol use disorder (AUD) and play a considerable role in the development and maintenance of alcohol dependence and relapse. Because of this high comorbidity, it is necessary to determine shared and unique genetic factors driving heavy drinking and negative affective behaviors. In order to identify novel pharmacogenetic targets, a bioinformatics analysis was used to quantify the expression of amygdala K+ channel genes that covary with anxiety-related phenotypes in the well-phenotyped and fully sequenced family of BXD strains. We used a model of stress-induced escalation of drinking in alcohol-dependent mice to measure negative affective behaviors during abstinence. A pharmacological approach was used to validate the key bioinformatics findings in alcohol-dependent, stressed mice. Amygdalar expression of Kcnn3 correlated significantly with 40 anxiety-associated phenotypes. Further examination of Kcnn3 expression revealed a strong eigentrait for anxiety-like behaviors and negative correlations with binge-like and voluntary alcohol drinking. Mice treated with chronic intermittent alcohol exposure and repeated swim stress consumed more alcohol in their home cages and showed hypophagia on the novelty-suppressed feeding test during abstinence. Pharmacologically targeting Kcnn gene products with the KCa2 (SK) channel-positive modulator 1-EBIO decreased drinking and reduced feeding latency in alcohol-dependent, stressed mice. Collectively, these validation studies provide central nervous system links into the covariance of stress, negative affective behaviors, and AUD in the BXD strains. Further, the bioinformatics discovery tool is effective in identifying promising targets (i.e., KCa2 channels) for treating alcohol dependence exacerbated by comorbid mood disorders.

scholarly journals Adult Neurogenesis in the Drosophila Brain: The Evidence and the Void

2020 ◽  
Vol 21 (18) ◽  
pp. 6653
Author(s):  
Guiyi Li ◽  
Alicia Hidalgo
Keyword(s):  
Adult Neurogenesis ◽  
Genetic Manipulation ◽  
Brain Plasticity ◽  
Fruit Fly ◽  
Cell Number ◽  
Adult Brain ◽  
Proliferating Cells ◽  
Drosophila Brain ◽  
The Central Nervous System ◽  
The Brain

Establishing the existence and extent of neurogenesis in the adult brain throughout the animals including humans, would transform our understanding of how the brain works, and how to tackle brain damage and disease. Obtaining convincing, indisputable experimental evidence has generally been challenging. Here, we revise the state of this question in the fruit-fly Drosophila. The developmental neuroblasts that make the central nervous system and brain are eliminated, either through apoptosis or cell cycle exit, before the adult fly ecloses. Despite this, there is growing evidence that cell proliferation can take place in the adult brain. This occurs preferentially at, but not restricted to, a critical period. Adult proliferating cells can give rise to both glial cells and neurons. Neuronal activity, injury and genetic manipulation in the adult can increase the incidence of both gliogenesis and neurogenesis, and cell number. Most likely, adult glio- and neuro-genesis promote structural brain plasticity and homeostasis. However, a definitive visualisation of mitosis in the adult brain is still lacking, and the elusive adult progenitor cells are yet to be identified. Resolving these voids is important for the fundamental understanding of any brain. Given its powerful genetics, Drosophila can expedite discovery into mammalian adult neurogenesis in the healthy and diseased brain.

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.

The ultrastructure of acinar cells in the external orbital gland of young and old male rats

1978 ◽  
Vol 36 (2) ◽  
pp. 276-277
Author(s):  
R. Carriere
Keyword(s):  
Young Adulthood ◽  
Acinar Cells ◽  
Cell Number ◽  
Male Rats ◽  
Polyploid Cell ◽  
Secretory Cells ◽  
Age Changes ◽  
Albino Rat ◽  
Golgi Membranes ◽  
Diploid Cells

The external orbital gland of the albino rat exhibits both sexual dimorphism and histological age changes. In males, many cells attain a remarkable degree of polyploidy and an increase of polyploid cell number constitutes the major age change until young adulthood. The acini of young adults have a small lumen and are composed of tall serous cells. Subsequently, many acini acquire a larger lumen with an irregular outline while numerous vacuoles accumulate throughout the secretory cells. At the same time, vesicular acini with a large lumen surrounded by pale-staining low cuboidal diploid cells begin to appear and their number increases throughout old age. The fine structure of external orbital glands from both sexes has been explored and in considering acinar cells from males, emphasis was given to the form of the Golgi membranes and to nuclear infoldings of cytoplasmic constituents.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

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