scholarly journals Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Nicole L. Reitz ◽  
Polliana T. Nunes ◽  
Lisa M. Savage
Keyword(s):  
Cognitive Impairment ◽  
Young Adult ◽  
Spontaneous Alternation ◽  
Ethanol Exposure ◽  
Hippocampal Neurogenesis ◽  
Male Rats ◽  
Middle Aged ◽  
Novel Object ◽  
Age Related ◽  
Spatial Tasks

Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25–55. Either 2 (young adult) or 12–14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.

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

Effect of aging on tracheal mucociliary clearance in beagle dogs

1987 ◽  
Vol 62 (3) ◽  
pp. 1331-1334 ◽  
Author(s):  
S. L. Whaley ◽  
B. A. Muggenburg ◽  
F. A. Seiler ◽  
R. K. Wolff
Keyword(s):  
Young Adult ◽  
Gamma Camera ◽  
Mucociliary Clearance ◽  
Age Groups ◽  
Beagle Dogs ◽  
Velocity Measurements ◽  
Middle Aged ◽  
Age Related ◽  
Age Related Changes ◽  
Made In

Tracheal mucous velocity measurements were made in 24 beagle dogs in five age groups, using a gamma camera to detect movement of instilled 99mTc-macroaggregated albumin. Age groups were defined as immature (9–10 mo), young adult (2.8–3.0 yr), middle aged (6.7–6.9 yr), mature (9.6–9.8 yr), and aged dogs (13.6–16.2 yr). Mean velocities were 3.6 +/- 0.4 (SE) mm/min in the immature dogs, 9.7 +/- 0.6 mm/min in the young adults, 6.9 +/- 0.5 mm/min in the middle-aged dogs, 3.5 +/- 0.8 mm/min in the mature dogs, and 2.9 +/- 0.5 mm/min in the aged dogs. Tracheal mucous velocity was significantly (P less than 0.05) greater in the young adult and middle-aged groups compared with the immature, mature, and aged dogs. This pattern of age-related changes was noted to be similar to age-related changes described for certain pulmonary function measurements.

Abstract 123: Age-Related Diminishment of the Subventricular Zone Cytogenic Response and Its Contributions to Motor Recovery After Cortical Infarcts

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michael R Williamson ◽  
Stephanie Le ◽  
Ronald L Franzen ◽  
Michael R Drew ◽  
Theresa A Jones
Keyword(s):  
Young Adult ◽  
Subventricular Zone ◽  
Motor Recovery ◽  
Lineage Tracing ◽  
Stem Cell Markers ◽  
Middle Aged ◽  
Reaching Task ◽  
Aged Mice ◽  
Adult Mice ◽  
Age Related

Stroke increases proliferation within the subventricular zone (SVZ) cytogenic niche and causes subsequent migration of newborn cells towards the site of injury. We investigated the functional consequences of age-related blunting of the SVZ cytogenic response to ischemia. We found that there was a marked reduction in proliferation and neural stem cell markers within the SVZ of middle aged (aged 12-16 months) versus young adult (aged 3-5 months) mice in the intact brain and after photothrombotic infarcts in motor cortex. Using an inducible, heritable lineage tracing system (Nestin-CreER T2 :: Ai14 mice) to quantify SVZ-derived neural precursor cells (NPCs) that migrated towards the infarct, we found that there was a considerable age-related reduction in the number of NPCs in peri-infarct cortex. These findings indicate a marked diminishment of SVZ NPC proliferation and migration after focal ischemia by middle age. Next, we assessed the contributions of the SVZ cytogenic response to recovery of skilled motor function. We used glial fibrillary acidic protein-thymidine kinase mice to conditionally ablate NPCs with ganciclovir administration. In young adult mice, NPC ablation significantly impaired recovery of motor performance on the single seed reaching task after motor cortical infarcts. By contrast, NPC ablation did not affect motor recovery in middle aged mice. Importantly, the magnitude of recovery was less in middle aged mice—regardless of NPC ablation—than in control young adult mice. Middle aged mice recovered similarly to young adult mice lacking NPCs. These results indicate that SVZ cytogenesis contributes to functional improvements after cortical infarcts and that the diminishment of the cytogenic response with age may be implicated in age-related worsening of outcome after stroke. Restoration of SVZ cytogenesis in aged animals might improve behavioral recovery.

scholarly journals Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner

2019 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Dwayne K. Hamson ◽  
Steven R. Wainwright ◽  
Carmen Chow ◽  
Jessica Chaiton ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Middle Aged ◽  
Young Males ◽  
Neuron Survival ◽  
Male And Female Rats ◽  
Age Dependent

AbstractAndrogens (testosterone and dihydrotestosterone) increase adult hippocampal neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone, a potent androgen, on neurogenesis in adult and middle-aged males and females. Rats were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU). The following day rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and new neuron survival (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased new neuron survival in young males but surprisingly not in middle-aged male rats. In females, DHT did not significantly affect adult neurogenesis in young or middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.

scholarly journals Targeting anticipatory neurogenesis to maintain cognitive reserve

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 198-199
Author(s):  
Amar Sahay
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Reserve ◽  
Hippocampal Neurogenesis ◽  
Neurogenic Niche ◽  
Memory Interference ◽  
Age Related ◽  
Adult Hippocampus ◽  
Age Related Cognitive Decline

Abstract Memory imprecision is a hallmark of age-related cognitive decline and mild-cognitive impairment (MCI) and is characterized by increased memory interference and decreased stability of memory representations. Evidence from humans, non-human primates and rodents demonstrate reduced hippocampal neurogenesis, excitation-inhibition imbalance and inflexible hippocampal remapping during age-related cognitive decline and MCI. Developing strategies to reverse cognitive decline during aging and Mild Cognitive Impairment necessitates an understanding of molecular, cellular, circuit and network mechanisms that support memory functions of the hippocampus. Over the last decade we have built a multifaceted program grounded in basic neuroscience that is aimed at improving memory in aging and MCI. We have demonstrated how we can Rejuvenate the aged hippocampus by selectively increasing neurogenesis and how we can Re-engineer connectivity of aged inhibitory microcircuits to improve memory precision in aging. Ongoing efforts include strategies to Repairing neurogenic niche fitness by targeting intercellular communication in the aging hippocampus. In today’s talk I will present a fourth approach catalyzed by our discovery of the first transcriptional regulator of neural stem cell expansion in the adult hippocampus. We will present data in support of this claim and convey how this discovery may guide strategies to maintain cognitive reserve embodied in the pool of neural stem cells in the adult hippocampus.

scholarly journals Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo

2019 ◽  
Vol 20 (3) ◽  
pp. 589 ◽  
Author(s):  
Maria Olmedillas del Moral ◽  
Nithi Asavapanumas ◽  
Néstor Uzcátegui ◽  
Olga Garaschuk
Keyword(s):  
Young Adult ◽  
Brain Aging ◽  
Critical Role ◽  
Low Grade ◽  
Middle Aged ◽  
Senescent Phenotype ◽  
Adult Mice ◽  
Age Related ◽  
Old Mice

Brain aging is characterized by a chronic, low-grade inflammatory state, promoting deficits in cognition and the development of age-related neurodegenerative diseases. Malfunction of microglia, the brain-resident immune cells, was suggested to play a critical role in neuroinflammation, but the mechanisms underlying this malfunctional phenotype remain unclear. Specifically, the age-related changes in microglial Ca2+ signaling, known to be linked to its executive functions, are not well understood. Here, using in vivo two-photon imaging, we characterize intracellular Ca2+ signaling and process extension of cortical microglia in young adult (2–4-month-old), middle-aged (9–11-month-old), and old (18–21-month-old) mice. Our data revealed a complex and nonlinear dependency of the properties of intracellular Ca2+ signals on an animal’s age. While the fraction of cells displaying spontaneous Ca2+ transients progressively increased with age, the frequencies and durations of the spontaneous Ca2+ transients followed a bell-shaped relationship, with the most frequent and largest Ca2+ transients seen in middle-aged mice. Moreover, in old mice microglial processes extending toward an ATP source moved faster but in a more disorganized manner, compared to young adult mice. Altogether, these findings identify two distinct phenotypes of aging microglia: a reactive phenotype, abundantly present in middle-aged animals, and a dysfunctional/senescent phenotype ubiquitous in old mice.

Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related

2012 ◽  
Vol 90 (10) ◽  
pp. 1372-1379 ◽  
Author(s):  
John C. Passmore ◽  
John T. Fleming ◽  
Suresh C. Tyagi ◽  
Jeff C. Falcone
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Tyrosine Kinase Receptor ◽  
Middle Aged ◽  
Male And Female Rats ◽  
Age Related

Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)3, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.

scholarly journals Mediterranean Natural Extracts Improved Cognitive Behavior in Zebrafish and Healthy Rats and Ameliorated LPS-induced Cognitive Impairment in a Sex Dependent Manner

2020 ◽  
Author(s):  
Matteo Pusceddu ◽  
Julia Hernandez-Baixauli ◽  
Francesc Puiggrós ◽  
Lluis Arola ◽  
Antoni Caimari ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mediterranean Diet ◽  
Female Rats ◽  
Male Rats ◽  
Cognitive Behavior ◽  
Dependent Manner ◽  
The Novel ◽  
Novel Object ◽  
Natural Extracts ◽  
The Mediterranean

Abstract Background: Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results: Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions: We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.

scholarly journals Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease

2019 ◽  
Vol 8 ◽  
pp. e1440
Author(s):  
Amir Hossein Zarifkar ◽  
Asadollah Zarifkar ◽  
Mohammad Nami ◽  
Ali Rafati ◽  
Hadi Aligholi ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Cognitive Impairment ◽  
Object Recognition ◽  
Alzheimer Disease ◽  
Cognitive Capacity ◽  
Male Rats ◽  
Transcranial Electrical Stimulation ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Exploration Time

Background: Treatment of Alzheimer as a disease that is associated with cognitive impairment has been associated with some restrictions. Recently, researchers have focused on non-pharmacological treatments, including non-invasive stimulation of the brain by transcranial electrical stimulation (tES). Four main paradigms of transcranial electrical current include transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial pulse current stimulation (tPCS). The tDCS is a possible new therapeutic option for patients with cognitive impairment, including Alzheimer disease. Materials and Methods: The study was done on Sprague-Dawley male rats weighing 250-270 g. to develop Alzheimer’s model, the cannula was implanted bilaterally into the hippocampus. Aβ 25-35 (5μg/ 2.5µl/day) was microinjected bilaterally for 4 days. Then, an electrical stimulation paradigm was applied to the animal for 6 days. Animal cognitive capacity was evaluated on day 11 and 12 by novel object recognition (NOR) test. Results: Our results showed that application of tDCS; tACS; tRNS and tPCS reversed beta-amyloid-induced impairment (P<0.05). The tRNS Group spent total exploration time around the objects compared to other groups (P<0.05). There was no significant difference between the four different paradigms in discrimination ratio and the percentage of total exploration time. Conclusion: The results of this study showed that the use of multiple sessions of different tES paradigms could improve Aβ-induced memory impairment in the NOR test. Therefore, based on evidence, it can be expected that in addition to using tDCS, other stimulatory paradigms may also be considered in the treatment of AD. [GMJ.2019;8:e1440]

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